The import and function of diatom and plant frataxins in the mitochondrion of Trypanosoma brucei

Czech Academy of Sciences Publication Activity Database

Long, Shaojun; Vávrová, Zuzana; Lukeš, Julius

2008-01-01

Roč. 162, č. 1 (2008), s. 100-104 ISSN 0166-6851 R&D Projects: GA AV ČR IAA500960705; GA MŠk LC07032; GA MŠk 2B06129; GA ČR GA204/06/1558 Institutional research plan: CEZ:AV0Z60220518 Keywords : frataxin * mitochondrion * Trypanosoma * diatom * evolutionary conservativeness * import Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.951, year: 2008

Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation

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Provvidenza Maria Abruzzo

2013-01-01

Full Text Available Friedreich’s ataxia (FRDA is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms (FXN-1, FXN-2, and FXN-3 in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex, and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor-γ (PPARG, PPARG expression was evaluated. At a low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms and that they may have a functional role.

Iron-induced oligomerization of human FXN^81-210 and bacterial CyaY frataxin and the effect of iron chelators

DEFF Research Database (Denmark)

Ahlgren, Eva Christina; Fekry, Mostafa; Wiemann, Mathias

2017-01-01

long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks...

Novel frataxin isoforms may contribute to the pathological mechanism of Friedreich ataxia.

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Haiyan Xia

Full Text Available Friedreich ataxia (FRDA is an inherited neurodegenerative disease caused by frataxin (FXN deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III, which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.

Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe-S cluster assembly centers.

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Galeano, B K; Ranatunga, W; Gakh, O; Smith, D Y; Thompson, J R; Isaya, G

2017-06-21

Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1. Here, in the absence of Yfh1, Isu1 was found to exist in two forms, one mostly monomeric with limited tendency to dimerize, and one with a strong propensity to oligomerize. Whereas the monomeric form is stabilized by zinc, the loss of zinc promotes formation of dimer and higher order oligomers. However, upon binding to oligomeric Yfh1, both forms take on a similar symmetrical trimeric configuration that places the Fe-S cluster coordinating residues of Isu1 in close proximity of iron-binding residues of Yfh1. This configuration is suitable for docking of Nfs1 in a manner that provides a structural context for coordinate iron and sulfur donation to the scaffold. Moreover, distinct structural features suggest that in physiological conditions the zinc-regulated abundance of monomeric vs. oligomeric Isu1 yields [Yfh1]·[Isu1] complexes with different Isu1 configurations that afford unique functional properties for Fe-S cluster assembly and delivery.

Selected missense mutations impair frataxin processing in Friedreich ataxia.

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Clark, Elisia; Butler, Jill S; Isaacs, Charles J; Napierala, Marek; Lynch, David R

2017-08-01

Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. Immunocytochemical studies and subcellular fractionation were performed to study FXN import into the mitochondria and examine the mechanism by which mutations impair FXN processing. Coimmunoprecipitation was performed to study the interaction between FXN and mitochondrial processing peptidase. A proteasome inhibitor was used to model traditional therapeutic strategies. In addition, clinical profiles of subjects with and without point mutations were compared in a large natural history study. FXN I 154F and FXN G 130V missense mutations decrease FXN 81-210 levels compared with FXN WT , FXN R 165C , and FXN W 155R , but do not block its association with mitochondria. FXN I 154F and FXN G 130V also impair FXN maturation and enhance the binding between FXN 42-210 and mitochondria processing peptidase. Furthermore, blocking proteosomal degradation does not increase FXN 81-210 levels. Additionally, impaired FXN processing also occurs in fibroblasts from patients with FXN G 130V . Finally, clinical data from patients with FXN G 130V and FXN I 154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia. These data suggest that the effects on processing associated with FXN G 130V and FXN I 154F mutations lead to higher levels of partially processed FXN, which may contribute to the milder clinical phenotypes in these patients.

Turning Escherichia coli into a Frataxin-Dependent Organism.

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Béatrice Roche

2015-05-01

Full Text Available Fe-S bound proteins are ubiquitous and contribute to most basic cellular processes. A defect in the ISC components catalyzing Fe-S cluster biogenesis leads to drastic phenotypes in both eukaryotes and prokaryotes. In this context, the Frataxin protein (FXN stands out as an exception. In eukaryotes, a defect in FXN results in severe defects in Fe-S cluster biogenesis, and in humans, this is associated with Friedreich's ataxia, a neurodegenerative disease. In contrast, prokaryotes deficient in the FXN homolog CyaY are fully viable, despite the clear involvement of CyaY in ISC-catalyzed Fe-S cluster formation. The molecular basis of the differing importance in the contribution of FXN remains enigmatic. Here, we have demonstrated that a single mutation in the scaffold protein IscU rendered E. coli viability strictly dependent upon a functional CyaY. Remarkably, this mutation changed an Ile residue, conserved in prokaryotes at position 108, into a Met residue, conserved in eukaryotes. We found that in the double mutant IscUIM ΔcyaY, the ISC pathway was completely abolished, becoming equivalent to the ΔiscU deletion strain and recapitulating the drastic phenotype caused by FXN deletion in eukaryotes. Biochemical analyses of the "eukaryotic-like" IscUIM scaffold revealed that it exhibited a reduced capacity to form Fe-S clusters. Finally, bioinformatic studies of prokaryotic IscU proteins allowed us to trace back the source of FXN-dependency as it occurs in present-day eukaryotes. We propose an evolutionary scenario in which the current mitochondrial Isu proteins originated from the IscUIM version present in the ancestor of the Rickettsiae. Subsequent acquisition of SUF, the second Fe-S cluster biogenesis system, in bacteria, was accompanied by diminished contribution of CyaY in prokaryotic Fe-S cluster biogenesis, and increased tolerance to change in the amino acid present at the 108th position of the scaffold.

Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

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Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

2014-06-27

Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice

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Belén Mollá

2017-08-01

Full Text Available Friedreich’s ataxia (FRDA is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux. The homogenous distribution of axonal spheroids along the neurites supports the existence of continues focal damages. This lead us to propose for FRDA a model of distal axonopathy based on axonal focal damages. In addition, we observed the involvement of oxidative stress and dyshomeostasis of calcium in axonal spheroid formation generating axonal injury as a primary cause of pathophysiology. Axonal spheroids may be a consequence of calcium imbalance, thus we propose the quenching or removal extracellular Ca2+ to prevent spheroids formation. In our neuronal model, treatments with BAPTA and o-phenanthroline reverted the axonal dystrophy and the mitochondrial dysmorphic parameters. These results support the hypothesis that axonal pathology is reversible in FRDA by pharmacological manipulation of intracellular Ca2+ with Ca2+ chelators or metalloprotease inhibitors, preventing Ca2+-mediated axonal injury. Thus, the modulation of Ca2+ levels may be a relevant therapeutic target to develop early axonal protection and prevent dying-back neurodegeneration.

Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).

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Seguin, Alexandra; Santos, Renata; Pain, Debkumar; Dancis, Andrew; Camadro, Jean-Michel; Lesuisse, Emmanuel

2011-02-25

Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Δyfh1) accumulate iron in the mitochondria in the form of nanoparticles of ferric phosphate. The phosphate content of Δyfh1 mitochondria was higher than that of wild-type mitochondria, but the proportion of mitochondrial phosphate that was soluble was much lower in Δyfh1 cells. The rates of phosphate and iron uptake in vitro by isolated mitochondria were higher for Δyfh1 than wild-type mitochondria, and a significant proportion of the phosphate and iron rapidly became insoluble in the mitochondrial matrix, suggesting co-precipitation of these species after oxidation of iron by oxygen. Increasing the amount of phosphate in the medium decreased the amount of iron accumulated by Δyfh1 cells and improved their growth in an iron-dependent manner, and this effect was mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier, MIR1, slightly increased the concentration of soluble mitochondrial phosphate and significantly improved various mitochondrial functions (cytochromes, [Fe-S] clusters, and respiration) in Δyfh1 cells. We conclude that in Δyfh1 cells, soluble phosphate is limiting, due to its co-precipitation with iron.

No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.

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Steinkellner, Hannes; Singh, Himanshu Narayan; Muckenthaler, Martina U; Goldenberg, Hans; Moganty, Rajeswari R; Scheiber-Mojdehkar, Barbara; Sturm, Brigitte

2017-07-20

Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported. Copyright © 2017 Elsevier B.V. All rights reserved.

Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes.

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Mysoon M Al-Ansari

Full Text Available BACKGROUND: Active cancer-associated fibroblasts (CAFs or myofibroblasts play important roles not only in the development and progression of breast carcinomas, but also in their prognosis and treatment. Therefore, targeting these cells through suppressing their supportive procarcinogenic paracrine effects is mandatory for improving the current therapies that are mainly targeting tumor cells. To this end, we investigated the effect of the natural and pharmacologically safe molecule, caffeine, on CAF cells and their various procarcinogenic effects. METHODOLOGY/PRINCIPAL FINDINGS: We have shown here that caffeine up-regulates the tumor suppressor proteins p16, p21, p53 and Cav-1, and reduces the expression/secretion of various cytokines (IL-6, TGF-β, SDF-1 and MMP-2, and down-regulates α-SMA. Furthermore, caffeine suppressed the migratory/invasiveness abilities of CAF cells through PTEN-dependent Akt/Erk1/2 inactivation. Moreover, caffeine reduced the paracrine pro-invasion/-migration effects of CAF cells on breast cancer cells. These results indicate that caffeine can inactivate breast stromal myofibroblasts. This has been confirmed by showing that caffeine also suppresses the paracrine pro-angiogenic effect of CAF cells through down-regulating HIF-1αand its downstream effector VEGF-A. Interestingly, these effects were sustained in absence of caffeine. CONCLUSION/SIGNIFICANCE: The present findings provide a proof of principle that breast cancer myofibroblasts can be inactivated, and thereby caffeine may provide a safe and effective prevention against breast tumor growth/recurrence through inhibition of the procarcinogenic effects of active stromal fibroblasts.

Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly.

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Cai, Kai; Frederick, Ronnie O; Tonelli, Marco; Markley, John L

2018-06-01

Frataxin (FXN) is involved in mitochondrial iron‑sulfur (Fe-S) cluster biogenesis and serves to accelerate Fe-S cluster formation. FXN deficiency is associated with Friedreich ataxia, a neurodegenerative disease. We have used a combination of isothermal titration calorimetry and multinuclear NMR spectroscopy to investigate interactions among the components of the biological machine that carries out the assembly of iron‑sulfur clusters in human mitochondria. Our results show that FXN tightly binds a single Fe 2+ but not Fe 3+ . While FXN (with or without bound Fe 2+ ) does not bind the scaffold protein ISCU directly, the two proteins interact mutually when each is bound to the cysteine desulfurase complex ([NFS1] 2 :[ISD11] 2 :[Acp] 2 ), abbreviated as (NIA) 2 , where "N" represents the cysteine desulfurase (NFS1), "I" represents the accessory protein (ISD11), and "A" represents acyl carrier protein (Acp). FXN binds (NIA) 2 weakly in the absence of ISCU but more strongly in its presence. Fe 2+ -FXN binds to the (NIA) 2 -ISCU 2 complex without release of iron. However, upon the addition of both l-cysteine and a reductant (either reduced FDX2 or DTT), Fe 2+ is released from FXN as consistent with Fe 2+ -FXN being the proximal source of iron for Fe-S cluster assembly. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.

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Piguet, Françoise; de Montigny, Charline; Vaucamps, Nadège; Reutenauer, Laurence; Eisenmann, Aurélie; Puccio, Hélène

2018-05-28

Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Mikkelsen, Jens D

2012-01-01

Long-term treatment with nicotine or selective α7 nicotinic acetylcholine receptor (nAChR) agonists increases the number of α7 nAChRs and this up-regulation may be involved in the mechanism underlying the sustained procognitive effect of these compounds. Here, we investigate the influence of type I...... expressing human α7 nAChR, whereas the type I PAMs AVL-3288 or NS1738 do not. Contrarily, neither type I nor II PAMs affect 10 μM nicotine-induced receptor up-regulation, suggesting that nicotine and A-582941 induce up-regulation through different mechanisms. We further show in vivo that 3 mg/kg PNU-120596...... is involved in A-582941-induced up-regulation. Our results are the first to show an in vivo difference between type I and II α7 nAChR PAMs, and demonstrate an agonist-dependent effect of type II PAMs occurring on a much longer time scale than previously appreciated. Furthermore, our data suggest that nicotine...

Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells

International Nuclear Information System (INIS)

Kito, Hiroaki; Yamazaki, Daiju; Ohya, Susumu; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2011-01-01

Highlights: → We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. → The ER stress facilitated the expression of inward rectifier K + channel (K ir 2.1) and induced sustained membrane hyperpolarization. → The membrane hyperpolarization induced sustained Ca 2+ entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. → The K ir 2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K + channel (K ir 2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K ir channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca 2+ concentration due to Ca 2+ influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K ir 2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

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Yuichiro Kikkawa

2014-01-01

Full Text Available Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH in rabbits. Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1 was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC preincubated with relaxin, myosin light chain phosphorylation (MLC was investigated with immunoblotting after endothelin-1 stimulation. Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC. Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm.

Long photoperiods sustain high pH in Arctic kelp forests.

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Krause-Jensen, Dorte; Marbà, Núria; Sanz-Martin, Marina; Hendriks, Iris E; Thyrring, Jakob; Carstensen, Jacob; Sejr, Mikael Kristian; Duarte, Carlos M

2016-12-01

Concern on the impacts of ocean acidification on calcifiers, such as bivalves, sea urchins, and foraminifers, has led to efforts to understand the controls on pH in their habitats, which include kelp forests and seagrass meadows. The metabolism of these habitats can lead to diel fluctuation in pH with increases during the day and declines at night, suggesting no net effect on pH at time scales longer than daily. We examined the capacity of subarctic and Arctic kelps to up-regulate pH in situ and experimentally tested the role of photoperiod in determining the capacity of Arctic macrophytes to up-regulate pH. Field observations at photoperiods of 15 and 24 hours in Greenland combined with experimental manipulations of photoperiod show that photoperiods longer than 21 hours, characteristic of Arctic summers, are conducive to sustained up-regulation of pH by kelp photosynthesis. We report a gradual increase in pH of 0.15 units and a parallel decline in pCO 2 of 100 parts per million over a 10-day period in an Arctic kelp forest over midsummer, with ample scope for continued pH increase during the months of continuous daylight. Experimental increase in CO 2 concentration further stimulated the capacity of macrophytes to deplete CO 2 and increase pH. We conclude that long photoperiods in Arctic summers support sustained up-regulation of pH in kelp forests, with potential benefits for calcifiers, and propose that this mechanism may increase with the projected expansion of Arctic vegetation in response to warming and loss of sea ice.

Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

DEFF Research Database (Denmark)

Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

2017-01-01

mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, whereas skeletal muscle was asymptomatic. In the KO heart, protein oxidation and a decreased glutathione...

Ceramide-induced TCR up-regulation

DEFF Research Database (Denmark)

Menné, C; Lauritsen, Jens Peter Holst; Dietrich, J

2000-01-01

to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase......The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein...... kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected...

Long photoperiods sustain high pH in Arctic kelp forests

DEFF Research Database (Denmark)

Krause-Jensen, Dorte; Marbà, Núria; Sanz-Martin, M.

2016-01-01

Concern on the impacts of ocean acidification on calcifiers, such as bivalves, sea urchins, and foraminifers, has led to efforts to understand the controls on pH in their habitats, which include kelp forests and seagrass meadows. The metabolism of these habitats can lead to diel fluctuation in pH...... with increases during the day and declines at night, suggesting no net effect on pH at time scales longer than daily. We examined the capacity of subarctic and Arctic kelps to up-regulate pH in situ and experimentally tested the role of photoperiod in determining the capacity of Arctic macrophytes to up......-regulate pH. Field observations at photoperiods of 15 and 24 hours in Greenland com- bined with experimental manipulations of photoperiod show that photoperiods longer than 21 hours, characteristic of Arctic summers, are conducive to sustained up-regulation of pH by kelp photosynthesis. We report a gradual...

Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Kito, Hiroaki [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Yamazaki, Daiju [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ohya, Susumu; Yamamura, Hisao [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

2011-07-29

Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

Upregulation of cyclooxygenase-2 expression in porcine macula densa with chronic nitric oxide synthase inhibition.

Science.gov (United States)

Kommareddy, M; McAllister, R M; Ganjam, V K; Turk, J R; Laughlin, M Harold

2011-11-01

The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.

Transcriptional Up-Regulation of APE1/Ref-1 in Hepatic Tumor: Role in Hepatocytes Resistance to Oxidative Stress and Apoptosis.

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Vittorio Di Maso

Full Text Available Human Hepatocellular Carcinoma (HCC is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD. Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1, a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC.In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH over-expressing APE1/Ref-1.APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis.APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.

Upregulation of Interleukin-33 in obstructive renal injury

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Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chang, Ya-Jen [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Su, Chia-Hao [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Tsai, Tzu-Hsien [Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chen, Shang-Der [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan (China); Yang, Jenq-Lin, E-mail: jyang@adm.cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China)

2016-05-13

Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.

Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease.

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Sirena Soriano

Full Text Available Friedreich's ataxia (FRDA, the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.

A combined nucleic acid and protein analysis in Friedreich ataxia: implications for diagnosis, pathogenesis and clinical trial design.

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Francesco Saccà

Full Text Available BACKGROUND: Friedreich's ataxia (FRDA is the most common hereditary ataxia among caucasians. The molecular defect in FRDA is the trinucleotide GAA expansion in the first intron of the FXN gene, which encodes frataxin. No studies have yet reported frataxin protein and mRNA levels in a large cohort of FRDA patients, carriers and controls. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 24 patients with classic FRDA phenotype (cFA, 6 late onset FRDA (LOFA, all homozygous for GAA expansion, 5 pFA cases who harbored the GAA expansion in compound heterozygosis with FXN point mutations (namely, p.I154F, c.482+3delA, p.R165P, 33 healthy expansion carriers, and 29 healthy controls. DNA was genotyped for GAA expansion, mRNA/FXN was quantified in real-time, and frataxin protein was measured using lateral-flow immunoassay in peripheral blood mononuclear cells (PBMCs. Mean residual levels of frataxin, compared to controls, were 35.8%, 65.6%, 33%, and 68.7% in cFA, LOFA, pFA and healthy carriers, respectively. Comparison of both cFA and pFA with controls resulted in 100% sensitivity and specificity, but there was overlap between LOFA, carriers and controls. Frataxin levels correlated inversely with GAA1 and GAA2 expansions, and directly with age at onset. Messenger RNA expression was reduced to 19.4% in cFA, 50.4% in LOFA, 52.7% in pFA, 53.0% in carriers, as compared to controls (p<0.0001. mRNA levels proved to be diagnostic when comparing cFA with controls resulting in 100% sensitivity and specificity. In cFA and LOFA patients mRNA levels correlated directly with protein levels and age at onset, and inversely with GAA1 and GAA2. CONCLUSION/SIGNIFICANCE: We report the first explorative study on combined frataxin and mRNA levels in PBMCs from a cohort of FRDA patients, carriers and healthy individuals. Lateral-flow immunoassay differentiated cFA and pFA patients from controls, whereas determination of mRNA in q-PCR was sensitive and specific only in cFA.

Interferon-β-induced activation of c-Jun NH2-terminal kinase mediates apoptosis through up-regulation of CD95 in CH31 B lymphoma cells

International Nuclear Information System (INIS)

Takada, Eiko; Shimo, Kuniaki; Hata, Kikumi; Abiake, Maira; Mukai, Yasuo; Moriyama, Masami; Heasley, Lynn; Mizuguchi, Junichiro

2005-01-01

Type I interferon (IFN)-induced antitumor action is due in part to apoptosis, but the molecular mechanisms underlying IFN-induced apoptosis remain largely unresolved. In the present study, we demonstrate that IFN-β induced apoptosis and the loss of mitochondrial membrane potential (ΔΨm) in the murine CH31 B lymphoma cell line, and this was accompanied by the up-regulation of CD95, but not CD95-ligand (CD95-L), tumor necrosis factor (TNF), or TNF-related apoptosis-inducing ligand (TRAIL). Pretreatment with anti-CD95-L mAb partially prevented the IFN-β-induced loss of ΔΨm, suggesting that the interaction of IFN-β-up-regulated CD95 with CD95-L plays a crucial role in the induction of fratricide. IFN-β induced a sustained activation of c-Jun NH 2 -terminal kinase 1 (JNK1), but not extracellular signal-regulated kinases (ERKs). The IFN-β-induced apoptosis and loss of ΔΨm were substantially compromised in cells overexpressing a dominant-negative form of JNK1 (dnJNK1), and it was slightly enhanced in cells carrying a constitutively active JNK construct, MKK7-JNK1 fusion protein. The IFN-β-induced up-regulation of CD95 together with caspase-8 activation was also abrogated in the dnJNK1 cells while it was further enhanced in the MKK7-JNK1 cells. The levels of cellular FLIP (c-FLIP), competitively interacting with caspase-8, were down-regulated by stimulation with IFN-β but were reversed by the proteasome inhibitor lactacystin. Collectively, the IFN-β-induced sustained activation of JNK mediates apoptosis, at least in part, through up-regulation of CD95 protein in combination with down-regulation of c-FLIP protein

Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

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Iva eBozic

2015-09-01

Full Text Available Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes – catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and •O2- production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells.

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Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

2015-01-01

Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes-catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and (·)O(-) 2 production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

Mechanisms of Hypoxic Up-Regulation of Versican Gene Expression in Macrophages.

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Fattah Sotoodehnejadnematalahi

Full Text Available Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM, and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold by long term hypoxia (5 days than by 1 day of hypoxia (48 fold. We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K, LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression.

Urinary Clusterin Is Upregulated in Nephropathia Epidemica

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Ekaterina V. Martynova

2018-01-01

Full Text Available Kidney insufficiency is a hallmark of nephropathia epidemica (NE. Little is known about the mechanisms of the NE kidney pathology, with current knowledge mainly based on findings in postmortem tissue. We have analyzed kidney damage biomarkers in urine collected from early- and late-phase NE using Bio-Plex kidney toxicity panels 1 and 2. To determine the disease specificity, kidney damage biomarkers were also analyzed in urine samples from patients diagnosed with gout, type 2 diabetes, systemic lupus erythematosus, and chronic kidney insufficiency. Analysis of 12 biomarkers suggests damage to the kidney proximal tubule at the onset of NE. Also, upregulation of biomarkers of inflammation and leukocyte chemotaxis were detected in NE urine. Furthermore, increased clusterin levels were found in early- and late-phase NE urine. Comparative analysis revealed that clusterin is a biomarker, upregulated in NE urine.

Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway.

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Singh, A S; Shah, A; Brockmann, A

2018-02-01

In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr-1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses. © 2017 The Royal Entomological Society.

Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients.

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Liangliang Niu

Full Text Available To evaluate the mRNA and protein expressions of NLRP3 inflammasome and its downstream inflammatory factors in human dry eye.We recruited 54 patients with Sjögren's syndrome dry eye (SSDE, 50 patients with non-Sjögren's syndrome dry eye (NSSDE, and 46 healthy controls. Tear film breakup time (TBUT, Schirmer I test, and fluorescein staining (FL were performed on all subjects. Tear samples were obtained to analyze the inflammatory cytokine levels of IL-1β and IL-18 via enzyme-linked immunosorbent (ELISA. Conjunctival impression cytology (CIC specimens were collected to detect the mRNA expression of NLRP3, caspase-1, IL-1β, and IL-18 using quantitative RT-PCR, and the protein expression of NLRP3 and caspase-1 by Western blotting.NLRP3 mRNA expression showed higher levels in both dry eye groups compared with controls, with a comparably significant elevation in the SSDE group (relative 2.47-fold upregulation, p<0.05. NLRP3 protein expression was also increased in SSDE group (relative1.94-fold upregulation compared with the controls. mRNA expression of caspase-1 was significantly upregulated in both SSDE (relative 1.44-fold upregulation, p<0.05 and NSSDE (relative 1.32-fold upregulation, p<0.05. Procaspase-1 protein level was increased in SSDE (relative 1.84-fold upregulation and NSSDE (relative 1.12-fold upregulation versus controls; and caspase-1 protein expression was also increased in SSDE (relative 1.49-fold upregulation and NSSDE (relative 1.17-fold upregulation compared with the controls. The patients with SSDE and NSSDE had higher IL-1β and IL-18 mRNA values and protein expressions than the controls did. The relative mRNA expression of IL-1β upregulated 3.59-fold (p<0.001 in SSDE and 2.13-fold (p<0.01 in NSSDE compared with the controls. IL-1β protein level also showed significant upregulation in SSDE (p=0.01; vs. controls groups. IL-18 mRNA expression levels were significantly upregulated in the SSDE (relative 2.97-fold upregulation, p

Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.

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Gong, Kerui; Jasmin, Luc

2017-02-01

It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

The emerging role of m-TOR up-regulation in brain Astrocytoma.

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Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

2017-05-01

The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

Genes Involved in Human Ribosome Biogenesis areTranscriptionally Upregulated in Colorectal Cancer

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Mansilla, Francisco; Lamy, Philippe; Ørntoft, Torben Falck

2009-01-01

Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p<10-3) when compared to normal mucosa. Overexpression was independent of microsate......Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p... of microsatellite status. The promoters of the genes studied showed a significant enrichment for several transcription factor binding sites. There was a significant correlation between the number of binding site targets for these transcription factors and the observed gene transcript upregulation. The upregulation...

Understanding the genetic and molecular pathogenesis of Friedreich’s ataxia through animal and cellular models

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Martelli, Alain; Napierala, Marek; Puccio, Hélène

2012-01-01

In 1996, a link was identified between Friedreich’s ataxia (FRDA), the most common inherited ataxia in men, and alterations in the gene encoding frataxin (FXN). Initial studies revealed that the disease is caused by a unique, most frequently biallelic, expansion of the GAA sequence in intron 1 of FXN. Since the identification of this link, there has been tremendous progress in understanding frataxin function and the mechanism of FRDA pathology, as well as in developing diagnostics and therapeutic approaches for the disease. These advances were the subject of the 4th International Friedreich’s Ataxia Conference held on 5th–7th May in the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. More than 200 scientists gathered from all over the world to present the results of research spanning all areas of investigation into FRDA (including clinical aspects, FRDA pathogenesis, genetics and epigenetics of the disease, development of new models of FRDA, and drug discovery). This review provides an update on the understanding of frataxin function, developments of animal and cellular models of the disease, and recent advances in trying to uncover potential molecules for therapy. PMID:22382366

Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.

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Elkington, Paul T G; Nuttall, Robert K; Boyle, Joseph J; O'Kane, Cecilia M; Horncastle, Donna E; Edwards, Dylan R; Friedland, Jon S

2005-12-15

Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.

Increased antigen presentation but impaired T cells priming after upregulation of interferon-beta induced by lipopolysaccharides is mediated by upregulation of B7H1 and GITRL.

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Fang Wang

Full Text Available Dendritic cells are able to present Ag-derived peptides on MHC class I and II molecules and induce T cells priming. Lipopolysaccharides (LPS, an activator of Toll-like 4 receptor (TLR4 signaling, has been demonstrated to facilitate Ag-presentation, up-regulate surface molecules expression but impair T cells priming. In this study, we investigated the effect of LPS on nicotine-enhanced DCs-dependent T cells priming and the mechanisms of LPS orchestrating the immunosuppressive program. We could demonstrate that the treatment with LPS resulted in increased surface molecules expression, enhanced Ag-presentation, up-regulated release of TGF-beta, TNF-alpha, IL-6, and IFN-beta. Concomititantly, the upregulation of IFN-beta in DCs induces the up-regulation of coinhibitory molecules B7H1 and GITRL, which cause an impaired activation of naïve Ag-specific T cells and the induction of T cell tolerance by enhancing B7H1-PD-1 interactions and promoting GITRL-GITL facilitated Treg generation, respectively. These data provide a mechanistic basis for the immunomodulatory action of IFN-beta which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune response and persistent infection.

Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection.

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Anthony Siau

Full Text Available Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface

Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes

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Philpott Michael P

2010-02-01

Full Text Available Abstract Background The human cell cycle transcription factor FOXM1 is known to play a key role in regulating timely mitotic progression and accurate chromosomal segregation during cell division. Deregulation of FOXM1 has been linked to a majority of human cancers. We previously showed that FOXM1 was upregulated in basal cell carcinoma and recently reported that upregulation of FOXM1 precedes malignancy in a number of solid human cancer types including oral, oesophagus, lung, breast, kidney, bladder and uterus. This indicates that upregulation of FOXM1 may be an early molecular signal required for aberrant cell cycle and cancer initiation. Results The present study investigated the putative early mechanism of UVB and FOXM1 in skin cancer initiation. We have demonstrated that UVB dose-dependently increased FOXM1 protein levels through protein stabilisation and accumulation rather than de novo mRNA expression in human epidermal keratinocytes. FOXM1 upregulation in primary human keratinocytes triggered pro-apoptotic/DNA-damage checkpoint response genes such as p21, p38 MAPK, p53 and PARP, however, without causing significant cell cycle arrest or cell death. Using a high-resolution Affymetrix genome-wide single nucleotide polymorphism (SNP mapping technique, we provided the evidence that FOXM1 upregulation in epidermal keratinocytes is sufficient to induce genomic instability, in the form of loss of heterozygosity (LOH and copy number variations (CNV. FOXM1-induced genomic instability was significantly enhanced and accumulated with increasing cell passage and this instability was increased even further upon exposure to UVB resulting in whole chromosomal gain (7p21.3-7q36.3 and segmental LOH (6q25.1-6q25.3. Conclusion We hypothesise that prolonged and repeated UVB exposure selects for skin cells bearing stable FOXM1 protein causes aberrant cell cycle checkpoint thereby allowing ectopic cell cycle entry and subsequent genomic instability. The aberrant

Sustainability.

Science.gov (United States)

Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

2016-10-01

This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.

Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation.

NARCIS (Netherlands)

Kucharekova, M.; Vissers, W.H.P.M.; Schalkwijk, J.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der

2003-01-01

The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol

Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells

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Katarina Znidar

2016-01-01

Full Text Available In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNβ mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16.F10 cells in culture, IFNβ mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA-dependent activator of interferon regulatory factor (DAI, DEAD (Asp-Glu-Ala-Asp box polypeptide 60 (DDX60, and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16.F10 cells, inducing effects in vitro and potentially in vivo.

DMPD: Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15331118 Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. Wu...e-associated up-regulation in macrophage PGE2 synthesis. PubmedID 15331118 Title Mechanism of age-associated... up-regulation in macrophage PGE2 synthesis. Authors Wu D, Meydani SN. Publicatio

Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.

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Hilda Ahnstedt

Full Text Available BACKGROUND AND PURPOSE: Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation. EXPERIMENTAL APPROACH: Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B, angiotensin II type 1 (AT1 and endothelin-1 type A and B (ETA and ETB receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression. KEY RESULTS: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture. CONCLUSIONS AND IMPLICATIONS: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.

Sustainable diets within sustainable food systems.

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Meybeck, Alexandre; Gitz, Vincent

2017-02-01

Sustainable diets and sustainable food systems are increasingly explored by diverse scientific disciplines. They are also recognised by the international community and called upon to orient action towards the eradication of hunger and malnutrition and the fulfilment of sustainable development goals. The aim of the present paper is to briefly consider some of the links between these two notions in order to facilitate the operationalisation of the concept of sustainable diet. The concept of sustainable diet was defined in 2010 combining two totally different perspectives: a nutrition perspective, focused on individuals, and a global sustainability perspective, in all its dimensions: environmental, economic and social. The nutrition perspective can be easily related to health outcomes. The global sustainability perspective is more difficult to analyse directly. We propose that it be measured as the contribution of a diet to the sustainability of food systems. Such an approach, covering the three dimensions of sustainability, enables identification of interactions and interrelations between food systems and diets. It provides opportunities to find levers of change towards sustainability. Diets are both the results and the drivers of food systems. The drivers of change for those variously involved, consumers and private individuals, are different, and can be triggered by different dimensions (heath, environment, social and cultural). Combining different dimensions and reasons for change can help facilitate the transition to sustainable diets, recognising the food system's specificities. The adoption of sustainable diets can be facilitated and enabled by food systems, and by appropriate policies and incentives.

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Energy Technology Data Exchange (ETDEWEB)

Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Jeong, Jieun; Wi, Anjin; Park, Whoashig [Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of); Han, Ho-jae [College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of); Park, Soo-hyun, E-mail: parksh@chonnam.ac.kr [College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

2015-06-05

Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.

Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

International Nuclear Information System (INIS)

Yeom, Chul-gon; Kim, Dong-il; Park, Min-jung; Choi, Joo-hee; Jeong, Jieun; Wi, Anjin; Park, Whoashig; Han, Ho-jae; Park, Soo-hyun

2015-01-01

Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats.

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Ding, Tan; Zhu, Chao; Kou, Zhen-Zhen; Yin, Jun-Bin; Zhang, Ting; Lu, Ya-Cheng; Wang, Li-Ying; Luo, Zhuo-Jing; Li, Yun-Qing

2014-09-01

To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid) (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.

Insecticide-Mediated Up-Regulation of Cytochrome P450 Genes in the Red Flour Beetle (Tribolium castaneum

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Xiao Liang

2015-01-01

Full Text Available Some cytochrome P450 (CYP genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively, permethrin (2.00- and 2.03-fold and lambda-cyhalothrin (1.73- and 1.81-fold, whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

Upregulation of LYAR induces neuroblastoma cell proliferation and survival.

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Sun, Yuting; Atmadibrata, Bernard; Yu, Denise; Wong, Matthew; Liu, Bing; Ho, Nicholas; Ling, Dora; Tee, Andrew E; Wang, Jenny; Mungrue, Imran N; Liu, Pei Y; Liu, Tao

2017-09-01

The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter. Genome-wide differential gene expression studies revealed that knocking down LYAR considerably upregulated the expression of oxidative stress genes including CHAC1, which depletes intracellular glutathione and induces oxidative stress. Although knocking down LYAR expression with siRNAs induced oxidative stress, neuroblastoma cell growth inhibition and apoptosis, co-treatment with the glutathione supplement N-acetyl-l-cysteine or co-transfection with CHAC1 siRNAs blocked the effect of LYAR siRNAs. Importantly, high levels of LYAR gene expression in human neuroblastoma tissues predicted poor event-free and overall survival in neuroblastoma patients, independent of the best current markers for poor prognosis. Taken together, our data suggest that LYAR induces proliferation and promotes survival of neuroblastoma cells by repressing the expression of oxidative stress genes such as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor in N-Myc oncogenesis.

Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

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Wijethilake, Chaminda

2017-07-01

This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing sustainable remediation frameworks using sustainability principles.

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Ridsdale, D Reanne; Noble, Bram F

2016-12-15

The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

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Adriana M Zimnicka

Full Text Available Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX, a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2 also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC. In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness.

Involvement of Prohibitin Upregulation in Abrin-Triggered Apoptosis

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Yu-Huei Liu

2012-01-01

Full Text Available Abrin (ABR, a protein purified from the seeds of Abrus precatorius, induces apoptosis in various types of cancer cells. However, the detailed mechanism remains largely uncharacterized. By using a cDNA microarray platform, we determined that prohibitin (PHB, a tumor suppressor protein, is significantly upregulated in ABR-triggered apoptosis. ABR-induced upregulation of PHB is mediated by the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK pathway, as demonstrated by chemical inhibitors. In addition, ABR significantly induced the expression of Bax as well as the activation of caspase-3 and poly(ADP-ribose polymerase (PARP in Jurkat T cells, whereas the reduction of PHB by specific RNA interference delayed ABR-triggered apoptosis through the proapoptotic genes examined. Moreover, our results also indicated that nuclear translocation of the PHB-p53 complex may play a role in the transcription of Bax. Collectively, our data show that PHB plays a role in ABR-induced apoptosis, which may be helpful for the development of diagnostic or therapeutic agents.

Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

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Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

2018-01-01

Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Corporate Sustainability Reporting in the BIST Sustainability Index

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Burcu Demirel

2016-11-01

Full Text Available In recent years, there is a growing focus on corporate operations especially since the publication of the first environmental reports in 1989. Companies have started to publish information about its environmental, social and sustainability policies. The study examines the sustainability reporting elements of Borsa Istanbul Sustainability Index (BIST in Turkey and to evaluate which elements is most vital in this context. This study will begin with the sustainability reporting that will be examined under the roof of corporation sustainability and end with the examination of sustainability reports of 15 firms, which are included in the BIST Sustainability Index in Turkey, and a content analysis. The reports of companies under study were taken from special web site and GRI (Global Reporting Initiative database of companies. Being the first study in examining the sustainability report of companies in BIST Sustainability Index, it is expected to contribute in literature about sustainability reporting recently started to gain importance in Turkey. Overall our findings suggest that the sustainability index established in Turkey is still in development stage, but the enterprises in the endeavor are working day by day to develop the sustainability qualities.

Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn.

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Sei, Hiroo; Oshima, Tadayuki; Shan, Jing; Wu, Liping; Yamasaki, Takahisa; Okugawa, Takuya; Kondo, Takashi; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

2016-01-01

Interleukin-33 (IL-33) is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS) have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn. The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed. IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels. Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.

Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn.

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Hiroo Sei

Full Text Available Interleukin-33 (IL-33 is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn.The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed.IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels.Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.

PPARGC1A is upregulated and facilitates lung cancer metastasis.

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Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

2017-10-15

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

Interdependences between sustainable development and sustainable economy

OpenAIRE

Emilia Mioara CÂMPEANU; Carmen Valentina RĂDULESCU

2014-01-01

Sustainable development and sustainable economy are mostly used concepts. Understanding clearly their meaning allows their use in an appropriate context and, therefore, their boundaries in terms of theoretical and practical approaches on which occasion it can be given their interdependencies. The paper aim is to analyze the interdependences between sustainable development and sustainable economy.

Osmotic stress upregulates the transcription of thiamine (vitamin B1 ...

African Journals Online (AJOL)

Osmotic stress upregulates the transcription of thiamine (vitamin B1) ... Oil palm's responses in terms of the expression profiles of these two thiamine biosynthesis genes to an osmotic stress inducer, polyethylene glycol ... from 32 Countries:.

Up-regulation of the Neuronal Nicotinic Receptor α7 by HIV Glycoprotein 120

Science.gov (United States)

Ballester, Leomar Y.; Capó-Vélez, Coral M.; García-Beltrán, Wilfredo F.; Ramos, Félix M.; Vázquez-Rosa, Edwin; Ríos, Raymond; Mercado, José R.; Meléndez, Roberto I.; Lasalde-Dominicci, José A.

2012-01-01

Approximately 30–50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV+ individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1-gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120IIIB on the expression and function of the nicotinic receptor α7 (α7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of α7-nAChRs. Because α7-nAChRs have a high permeability to Ca2+, we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist α-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the α7-nAChR in gp120-transgenic mice brains. Specifically, α7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV+ patients. In summary, CXCR4 activation induces up-regulation of α7-nAChR, causing cell death, suggesting that α7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection. PMID:22084248

Fluoride Stimulates the Proliferation of Osteoclasts in vitro by Upregulating MCM3

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Shengbin Bai

2016-06-01

Full Text Available We have previously shown that the expression of the minichromosome maintenance protein 3 (MCM3 gene was upregulated in lymphocytes of patients with skeletal fluorosis. We speculated that increased MCM3 expression may be contribute to osteopathy in patients with skeletal fluorosis. Here, we investigated the effect of fluoride on the proliferation of osteoclasts derived from RAW264.7 cells and the involvement of MCM3. Our MTT assays showed that 0.25 mM NaF markedly stimulated the proliferation of RAW264.7 cells. The RT-PCR and immunoblotting assays revealed that 0.25 mM NaF upregulated MCM3 expression in RAW264.7 cells. The MTT assays additionally demonstrated that stimulation with MCM3 potentiated the effect of fluorine on the proliferation of RAW264.7 cells. These results demonstrated that fluoride at clinical relevant concentration upregulates MCM3 expression in osteoclasts in vitro. We are currently conducting a series of experiments to examine whether increased MCM3 in osteoclasts indeed contributes to osteopathy in skeletal fluorosis.

LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma.

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Yun-Bo, Feng; Xiao-Po, Liu; Xiao-Li, Li; Guo-Long, Cao; Pei, Zhang; Fa-Ming, Tian

2016-01-01

To examine the expression and function of long non-coding RNA taurine up-regulated 1 ( TUG1 ) in human osteosarcoma cells. Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1 , since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

Neutral endopeptidase up-regulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

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Pelorosso, Facundo Germán; Halperin, Ana Verónica; Palma, Alejandro Martín; Nowak, Wanda; Errasti, Andrea Emilse; Rothlin, Rodolfo Pedro

2007-02-01

Previous reports show that bradykinin B(2) receptors mediate contractile responses induced by bradykinin (BK) in human umbilical artery (HUA). However, although it has been reported that BK-induced responses can desensitize in several inflammatory models, the effects of prolonged in vitro incubation on BK-induced vasoconstriction in HUA have not been studied. In isolated HUA rings, BK-induced responses after a 5-h in vitro incubation showed a marked desensitization compared with responses at 2 h. Inhibition of either angiotensin-converting enzyme (ACE) or neutral endopeptidase (NEP), both BK-inactivating enzymes, failed to modify responses to BK at 2 h. After 5 h, ACE inhibition produced only a slight potentiation of BK-induced responses. In contrast, BK-induced vasoconstriction at 5 h was markedly potentiated by NEP inhibition. Moreover, NEP activity, measured by hydrolysis of its synthetic substrate (Z-Ala-Ala-Leu-p-nitroanilide), showed a 2.4-fold increase in 5-h incubated versus 2-h incubated tissues, which was completely reversed by cycloheximide (CHX) treatment. Furthermore, CHX significantly potentiated BK-induced responses, suggesting that NEP-mediated kininase activity increase at 5 h depends on de novo protein synthesis. In addition, under NEP inhibition, CHX treatment failed to produce an additional potentiation of BK-induced vasoconstriction. Still, NEP up-regulation was confirmed by Western blot, showing a 2.1-fold increase in immunoreactive NEP in 5-h incubated versus 2-h incubated HUA. In summary, the present study provides strong pharmacological evidence that NEP is up-regulated and plays a key role in desensitization of BK-induced vasoconstriction after prolonged in vitro incubation in HUA. Our results provide new insights into the possible mechanisms involved in BK-induced response desensitization during sustained inflammatory conditions.

Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

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Hossein Mostafavi

2014-02-01

Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

Atomistic mechanism of microRNA translation upregulation via molecular dynamics simulations.

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Wei Ye

Full Text Available MicroRNAs are endogenous 23-25 nt RNAs that play important gene-regulatory roles in animals and plants. Recently, miR369-3 was found to upregulate translation of TNFα mRNA in quiescent (G0 mammalian cell lines. Knock down and immunofluorescence experiments suggest that microRNA-protein complexes (with FXR1 and AGO2 are necessary for the translation upregulation. However the molecular mechanism of microRNA translation activation is poorly understood. In this study we constructed the microRNA-mRNA-AGO2-FXR1 quadruple complex by bioinformatics and molecular modeling, followed with all atom molecular dynamics simulations in explicit solvent to investigate the interaction mechanisms for the complex. A combined analysis of experimental and computational data suggests that AGO2-FXR1 complex relocalize microRNA:mRNA duplex to polysomes in G0. The two strands of dsRNA are then separated upon binding of AGO2 and FXR1. Finally, polysomes may improve the translation efficiency of mRNA. The mutation research confirms the stability of microRNA-mRNA-FXR1 and illustrates importance of key residue of Ile304. This possible mechanism can shed more light on the microRNA-dependent upregulation of translation.

Grassland Sustainability

Science.gov (United States)

Deborah U. Potter; Paulette L. Ford

2004-01-01

In this chapter we discuss grassland sustainability in the Southwest, grassland management for sustainability, national and local criteria and indicators of sustainable grassland ecosystems, and monitoring for sustainability at various scales. Ecological sustainability is defined as: [T]he maintenance or restoration of the composition, structure, and processes of...

Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

Science.gov (United States)

2012-01-01

Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury

International Nuclear Information System (INIS)

Jung, Michaela; Hotter, Georgina; Vinas, Jose Luis; Sola, Anna

2009-01-01

The mitochondria are a critical target for cisplatin-associated nephrotoxicity. Though nitric oxide formation has been implicated in the toxicity of cisplatin, this formation has not so far been related to a possible activation of mitochondrial nitric oxide synthase (mNOS). We show here that the upregulation of oxide mNOS and peroxynitrite formation in cisplatin treatment are key events that influence the development of the harmful parameters described in cisplatin-associated kidney failure. We confirm this by isolating the mitochondrial fraction of the kidney and across different access routes such as the use of a specific inhibitor of neuronal NOS, L-NPA, a peroxynitrite scavenger, FeTMPyP, and a peroxynitrite donor, SIN-1. The in vitro studies corroborated the information obtained in the in vivo experiments. The administration of cisplatin reveals a clear upregulation in the transcription of neuronal NOS and an increase in the levels of nitrites in the mitochondrial fractions of the kidneys. The upregulated transcription directly affects the cytoskeleton structure and the apoptosis. The inhibition of neuronal NOS reduces the levels of nitrites, cell death, and cytoskeleton derangement. Peroxynitrite is involved in the mechanism promoting the NOS transcription. In addition, in controls SIN-1 imitates the effects of cisplatin. In summary, we demonstrate that upregulation of mNOS in cisplatin treatment is a key component in both the initiation and the spread of cisplatin-associated damage in the kidney. Furthermore, peroxynitrite formation is directly involved in this process

Textiles and clothing sustainability sustainable technologies

CERN Document Server

2017-01-01

This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma

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Yun-Bo Feng

2016-01-01

Full Text Available Objective: To examine the expression and function of long non-coding RNA taurine up-regulated 1 (TUG1 in human osteosarcoma cells. Methods: Real-time quantitive PCR was used to detect the transcription level of TUG1 in a series of osteosarcoma cell lines. Knockdown of TUG1 in U2OS cells was carried out by transient transfection of siRNAs. MTT assay was performed to access the cell growth rates. Afterwards, RNA and protein of these cells were extracted to analyze the transfection efficient as well as the expression of other molecules. Results: Compared to the normal cell line, TUG1 exhibited a significant upregulation in osteosarcoma cells. Phenotyping analysis showed the growth-promotion activity of TUG1, since knockdown of TUG1 resulted in declined proliferation. We also found that AKT phosphorylation was impaired after TUG1 was inhibited, suggesting that the AKT pathway was involved in the regulation of TUG1 in U2OS cells. Conclusion: Our data provided evidence that TUG1 was upregulated and acted as a possible oncogene via positively regulating cell proliferation in osteosarcoma cells.

The Influence of Emotion Upregulation on the Expectation of Sexual Reward.

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Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Trimbos, Baptist; Both, Stephanie

2016-01-01

Emotion regulation research has shown successful altering of unwanted aversive emotional reactions. Cognitive strategies can also downregulate expectations of reward arising from conditioned stimuli, including sexual stimuli. However, little is known about whether such strategies can also efficiently upregulate expectations of sexual reward arising from conditioned stimuli, and possible gender differences therein. The present study examined whether a cognitive upregulatory strategy could successfully upregulate sexual arousal elicited by sexual reward-conditioned cues in men and women. Men (n = 40) and women (n = 53) participated in a study using a differential conditioning paradigm, with genital vibrostimulation as unconditioned stimulus (US) and sexually relevant pictures as conditional stimuli. Penile circumference and vaginal pulse amplitude were assessed and ratings of US expectancy, affective value, and sexual arousal value were obtained. Also a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. Evidence was found for emotion upregulation to increase genital arousal response in the acquisition phase in both sexes, and to enhance resistance to extinction of conditioned genital responding in women. In men, the emotion upregulatory strategy resulted in increased conditioned positive affect. The findings support that top-down modulation may indeed influence conditioned sexual responses. This knowledge may have implications for treating disturbances in sexual appetitive responses, such as low sexual arousal and desire. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The sustainable company: new challenges and strategies for more sustainability

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Victor DANCIU

2013-09-01

Full Text Available The sustainability becomes a model of development only if countries, industries, businesses and citizens become sustainable. The contribution of the business to a promising future should come from a fully integrated sustainability in its DNA and strategies.This paper focuses on the needed sustainable strategies for scaling up the contribution of the companies to sustainable development in the future. At the beginning, we analyze the main theoretical points of view on sustainability. Then, we explain how companies could achieve the sustainability by following the steps of a difficult process and the present performances in sustainability of large companies around the world. Finally, we suggest four strategies that businesses could design and implement in order to scaling up their sustainability in the future.The research has two important conclusions on sustainability in business. One is that the sustainability pays off if it is integrated in the DNA of the companies. The other conclusion says that the companies will succeed to make the needed transformation for achieving a better sustainability in the future only if they design and perform strategies focused on improving sustainability.

Reference: 475 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available n higher plants, we analyze two knock-out and one knock-down T-DNA insertion mutants. The knock...-out mutants present an embryo-lethal phenotype, indicating an essential role for frataxin. The knock

Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats.

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Morten S Thomsen

Full Text Available The α7 nicotinic acetylcholine receptor (nAChR is a potential target for the treatment of cognitive deficits in patients with schizophrenia, ADHD and Alzheimer's disease. Here we test the hypothesis that upregulation of α7 nAChR levels underlies the enhanced and sustained procognitive effect of repeated administration of α7 nAChR agonists. We further compare the effect of agonists to that of α7 nAChR positive allosteric modulators (PAMs, which do not induce upregulation of the α7 nAChR. Using the social discrimination test as a measure of short-term memory, we show that the α7 nAChR agonist A-582941 improves short-term memory immediately after repeated (7× daily, but not a single administration. The α7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects of agonists and PAMs that may be relevant for clinical development. Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration, suggesting that repeated administration of both agonists and PAMs may produce sustained effects on cognitive performance. Subsequent [(125I]-bungarotoxin autoradiography revealed no direct correlation between α7 nAChR levels in frontal cortical or hippocampal brain regions and short-term memory with either compound. Additionally, repeated treatment with A-582941 did not affect mRNA expression of RIC-3 or the lynx-like gene products lynx1, lynx2, PSCA, or Ly6H, which are known to affect nAChR function. In conclusion, both α7 nAChR agonists and PAMs exhibit sustained pro-cognitive effects after repeated administration, and altered levels of the α7 nAChR per se, or that of endogenous regulators of nAChR function, are likely not the major cause of this effect.

Sustainable flood risk management – What is sustainable?

DEFF Research Database (Denmark)

Sørup, Hjalte Jomo Danielsen; Brudler, Sarah; Lerer, Sara Maria

2016-01-01

Sustainable flood risk management has to be achieved since flood protection is a fundamental societal service that we must deliver. Based on the discourse within the fields of risk management and sustainable urban water management, we discuss the necessity of assessing the sustainability of flood...... risk management, and propose an evaluation framework for doing so. We argue that it is necessary to include quantitative sustainability measures in flood risk management in order to exclude unsustainable solutions. Furthermore, we use the concept of absolute sustainability to discuss the prospects...... of maintaining current service levels without compromising future generation’s entitlement of services. Discussions on the sustainability of different overall flood risk schemes must take place. Fundamental changes in the approaches will require fundamental changes in the mind-sets of practitioners as well...

Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells

International Nuclear Information System (INIS)

Lee, Ha Young; Kim, Mi-Kyoung; Park, Kyoung Sun; Bae, Yun Hee; Yun, Jeanho; Park, Joo-In; Kwak, Jong-Young; Bae, Yoe-Sik

2005-01-01

In the present study, we found that serum amyloid A (SAA) stimulated matrix-metalloproteinase-9 (MMP-9) upregulation at the transcription and translational levels in THP-1 cells. SAA stimulated the activation of nuclear factor κB (NF-κB), which was required for the MMP-9 upregulation by SAA. The signaling events induced by SAA included the activation of ERK and intracellular calcium rise, which were found to be required for MMP-9 upregulation. Formyl peptide receptor like 1 (FPRL1) was found to be involved in the upregulation of MMP-9 by SAA. Among several FPRL1 agonists, including Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), SAA selectively stimulated MMP-9 upregulation. With respect to the molecular mechanisms involved in the differential action of SAA and WKYMVm, we found that SAA could not competitively inhibit the binding of 125 I-labeled WKYMVm to FPRL1. Taken together, we suggest that SAA plays a role in the modulation of inflammatory and immune responses via FPRL1, by inducing MMP-9 upregulation in human monocytic cells

Sustainable Lifestyle Marketing of Individuals: the Base of Sustainability

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Mira Rakic

2015-08-01

Full Text Available This paper highlights the sustainable lifestyle marketing of an individual (SLMOI. The SLMOI is the activity, a set of institutions and processes for creating, communicating and maintaining the sustainable lifestyle of an individual (SLOI. The SLOI is an individual’s sustainability-oriented pattern of living represented by his or her activities, interests and opinions. The SLOI refers to a sustainable pattern of life (daily activities within the family, a sustainable pattern of consumption, a sustainable pattern of work and production (as employees in organizations and a sustainable pattern of behavior in the society and the environment they live in. The SLOI reflects an individual’s choices with respect to spending time, money and energy in accordance with the sustainable pattern of life. The SLOI stands for sustainable behavioral patterns on the basis of attitudes and values. The purpose of this paper is to investigate the attitudes of the population towards sustainable lifestyles and the SLMOI (performed by different actors and behaviors on the basis of attitudes.Using a face-to-face questionnaire interview, the study was conducted on a sample of 400 citizens of Serbia. There are three key conclusions. First, the SLMOI leads to the SLOI, and the SLOI further leads to sustainability. Second, the creation and maintenance of the SLOI is a long-term process. Third, a holistic approach is needed as well as the engagement of numerous actors in that process of creating and maintaining the SLOI.

Textiles and clothing sustainability sustainable fashion and consumption

CERN Document Server

2017-01-01

This is the first book to introduce and explain the concept of sustainable consumption with reference to the clothing sector. It uses various case studies to detail sustainable consumption behavior in the industry. Consumption is a key issue and is a major driver when it comes to sustainability in any industry, including clothing sector. Several studies which have highlighted the need for sustainable consumption in the clothing sector are discussed in this book.

Nicotine induces cell proliferation in association with cyclin D1 up-regulation and inhibits cell differentiation in association with p53 regulation in a murine pre-osteoblastic cell line

International Nuclear Information System (INIS)

Sato, Tsuyoshi; Abe, Takahiro; Nakamoto, Norimichi; Tomaru, Yasuhisa; Koshikiya, Noboru; Nojima, Junya; Kokabu, Shoichiro; Sakata, Yasuaki; Kobayashi, Akio; Yoda, Tetsuya

2008-01-01

Recent studies have suggested that nicotine critically affects bone metabolism. Many studies have examined the effects of nicotine on proliferation and differentiation, but the underlying molecular mechanisms remain unclear. We examined cell cycle regulators involved in the proliferation and differentiation of MC3T3-E1 cells. Nicotine induced cell proliferation in association with p53 down-regulation and cyclin D1 up-regulation. In differentiated cells, nicotine reduced alkaline phosphatase activity and mineralized nodule formation in dose-dependent manners. Furthermore, p53 expression was sustained in nicotine-treated cells during differentiation. These findings indicate that nicotine promotes the cell cycle and inhibits differentiation in association with p53 regulation in pre-osteoblastic cells

Sustainable markets for sustainable energy

Energy Technology Data Exchange (ETDEWEB)

Millan, J.; Smyser, C.

1997-12-01

The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

Textiles and clothing sustainability sustainable textile chemical processes

CERN Document Server

2017-01-01

This book highlights the challenges in sustainable wet processing of textiles, natural dyes, enzymatic textiles and sustainable textile finishes. Textile industry is known for its chemical processing issues and many NGO’s are behind the textile sector to streamline its chemical processing, which is the black face of clothing and fashion sector. Sustainable textile chemical processes are crucial for attaining sustainability in the clothing sector. Seven comprehensive chapters are aimed to highlight these issues in the book.

Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules.

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Glasner, Ariella; Oiknine-Djian, Esther; Weisblum, Yiska; Diab, Mohammad; Panet, Amos; Wolf, Dana G; Mandelboim, Ofer

2017-11-15

NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity, and even pregnancy and that specialize in antiviral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower inhibitory signals. The NK cell inhibitory receptors include a uniquely diverse array of proteins named killer cell immunoglobulin-like receptors (KIRs), the CD94 family, and the leukocyte immunoglobulin-like receptor (LIR) family. The NK cell inhibitory receptors recognize mostly major histocompatibility complex (MHC) class I (MHC-I) proteins. Zika virus has recently emerged as a major threat due to its association with birth defects and its pandemic potential. How Zika virus interacts with the immune system, and especially with NK cells, is unclear. Here we show that Zika virus infection is barely sensed by NK cells, since little or no increase in the expression of activating NK cell ligands was observed following Zika infection. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to the inhibition of NK cell killing. Mechanistically, we show that MHC class I proteins are upregulated via the RIGI-IRF3 pathway and that this upregulation is mediated via beta interferon (IFN-β). Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus. IMPORTANCE NK cells are innate lymphocytes that recognize and eliminate various pathogens and are known mostly for their role in controlling viral infections. NK cells express inhibitory and activating receptors, and they kill or spare their targets based on the integration of inhibitory and activating signals. Zika virus has recently emerged as a major threat to humans due to its pandemic potential and its association with birth defects. The role of NK cells in Zika virus

Conceptualising sustainability assessment

International Nuclear Information System (INIS)

Pope, Jenny; Annandale, David; Morrison-Saunders, Angus

2004-01-01

Sustainability assessment is being increasingly viewed as an important tool to aid in the shift towards sustainability. However, this is a new and evolving concept and there remain very few examples of effective sustainability assessment processes implemented anywhere in the world. Sustainability assessment is often described as a process by which the implications of an initiative on sustainability are evaluated, where the initiative can be a proposed or existing policy, plan, programme, project, piece of legislation, or a current practice or activity. However, this generic definition covers a broad range of different processes, many of which have been described in the literature as 'sustainability assessment'. This article seeks to provide some clarification by reflecting on the different approaches described in the literature as being forms of sustainability assessment, and evaluating them in terms of their potential contributions to sustainability. Many of these are actually examples of 'integrated assessment', derived from environmental impact assessment (EIA) and strategic environmental assessment (SEA), but which have been extended to incorporate social and economic considerations as well as environmental ones, reflecting a 'triple bottom line' (TBL) approach to sustainability. These integrated assessment processes typically either seek to minimise 'unsustainability', or to achieve TBL objectives. Both aims may, or may not, result in sustainable practice. We present an alternative conception of sustainability assessment, with the more ambitious aim of seeking to determine whether or not an initiative is actually sustainable. We term such processes 'assessment for sustainability'. 'Assessment for sustainability' firstly requires that the concept of sustainability be well-defined. The article compares TBL approaches and principles-based approaches to developing such sustainability criteria, concluding that the latter are more appropriate, since they avoid many

Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

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Kao Ming-Ching

2011-02-01

Full Text Available Abstract Background Hyperbaric oxygen therapy (HBOT is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS, is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.

Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells.

Science.gov (United States)

Wu, Jia; Ji, Xiaowei; Zhu, Linlin; Jiang, Qiaoli; Wen, Zhenzhen; Xu, Song; Shao, Wei; Cai, Jianting; Du, Qin; Zhu, Yongliang; Mao, Jianshan

2013-02-28

Abnormal cytokinesis increases the possibility of nuclear fusion in tumor cells. However, the role of microRNAs (miRNAs) in abnormal cytokinesis is unclear. Here, we found that miR-1290 was significantly up-regulated in clinical colon cancer tissues. Up-regulation of miR-1290 postponed cytokinesis and led to the formation of multinucleated cells. KIF13B was a target of miR-1290 that was involved in aberrant cytokinesis. Furthermore, enforced expression of miR-1290 activated the Wnt pathway and increased the reprogramming-related transcript factors c-Myc and Nanog. Our results suggest that up-regulation of miR-1290 in colon cancer cells impaired cytokinesis and affected reprogramming. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

MicroRNA-276 promotes egg-hatching synchrony by up-regulating brm in locusts

Science.gov (United States)

He, Jing; Chen, Qianquan; Wei, Yuanyuan; Jiang, Feng; Yang, Meiling; Hao, Shuguang; Guo, Xiaojiao; Chen, Dahua; Kang, Le

2016-01-01

Developmental synchrony, the basis of uniform swarming, migration, and sexual maturation, is an important strategy for social animals to adapt to variable environments. However, the molecular mechanisms underlying developmental synchrony are largely unexplored. The migratory locust exhibits polyphenism between gregarious and solitarious individuals, with the former displaying more synchronous sexual maturation and migration than the latter. Here, we found that the egg-hatching time of gregarious locusts was more uniform compared with solitarious locusts and that microRNA-276 (miR-276) was expressed significantly higher in both ovaries and eggs of gregarious locusts than in solitarious locusts. Interestingly, inhibiting miR-276 in gregarious females and overexpressing it in solitarious females, respectively, caused more heterochronic and synchronous hatching of progeny eggs. Moreover, miR-276 directly targeted a transcription coactivator gene, brahma (brm), resulting in its up-regulation. Knockdown of brm not only resulted in asynchronous egg hatching in gregarious locusts but also impaired the miR-276–induced synchronous egg hatching in solitarious locusts. Mechanistically, miR-276 mediated brm activation in a manner that depended on the secondary structure of brm, namely, a stem-loop around the binding site of miR-276. Collectively, our results unravel a mechanism by which miR-276 enhances brm expression to promote developmental synchrony and provide insight into regulation of developmental homeostasis and population sustaining that are closely related to biological synchrony. PMID:26729868

Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

Energy Technology Data Exchange (ETDEWEB)

Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

2014-11-15

Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

Airborne fine particulate matter induces an upregulation of endothelin receptors on rat bronchi

International Nuclear Information System (INIS)

Wang, Rong; Xiao, Xue; Cao, Lei; Shen, Zhen-xing; Lei, Ying; Cao, Yong-xiao

2016-01-01

Airborne fine particulate matter (PM2.5) is a risk factor for respiratory diseases. However, little is known about the effects of PM2.5 on bronchi. The present study investigated the effect of airborne PM2.5 on rat bronchi and the underlying mechanisms. Isolated rat bronchial segments were cultured for 24 h. Endothelin (ET) receptor-mediated contractile responses were recorded using a wire myograph. The mRNA and protein expression levels of ET receptors were studied using quantitative real-time PCR, Western blotting, and immunohistochemistry. The results demonstrated that ET A and ET B receptor agonists induced remarkable contractile responses on fresh and cultured bronchial segments. PM2.5 (1.0 or 3.0 μg/ml) significantly enhanced ET A and ET B receptor-mediated contractile responses in bronchi with a markedly increased maximal contraction compared to the DMSO or fresh groups. PM2.5 increased the mRNA and protein expression levels of ET A and ET B receptors. U0126 (a MEK1/2 inhibitor) and SB203580 (a p38 inhibitor) significantly suppressed PM2.5-induced increases in ET B receptor-mediated contractile responses, mRNA and protein levels. SP600125 (a JNK inhibitor) and SB203580 significantly abrogated the PM2.5-induced enhancement of ET A receptor-mediated contraction and receptor expression. In conclusion, PM2.5 upregulates ET receptors in bronchi. ET B receptor upregulation is associated with MEK1/2 and p38 pathways, and the upregulation of ET A receptor is involved in JNK and p38 pathways. - Highlights: • Airborne PM2.5 induces bronchial hyperreactivity mediated with endothelin ET B and ET A receptors in rats. • PM2.5 increases mRNA and protein expressions of endothelin ET B and ET A receptors in bronchi. • The upregulation of ET B receptor is associated with MEK1/2 and p38 pathways. • The upregulation of ET A receptor is involved in JNK and p38 pathways. • The research provides novel understanding for PM2.5-associated respiratory diseases.

Sustainable Disruptions

DEFF Research Database (Denmark)

Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

2016-01-01

Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

Smart Sustainable Islands VS Smart Sustainable Cities

Science.gov (United States)

Pantazis, D. N.; Moussas, V. C.; Murgante, B.; Daverona, A. C.; Stratakis, P.; Vlissidis, N.; Kavadias, A.; Economou, D.; Santimpantakis, K.; Karathanasis, B.; Kyriakopoulou, V.; Gadolou, E.

2017-09-01

This paper has several aims: a) the presentation of a critical analysis of the terms "smart sustainable cities" and "smart sustainable islands" b) the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors) which concern the insular municipalities c) the creation of an island's smartification and sustainability index d) the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e) the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

SMART SUSTAINABLE ISLANDS VS SMART SUSTAINABLE CITIES

Directory of Open Access Journals (Sweden)

D. N. Pantazis

2017-09-01

Full Text Available This paper has several aims: a the presentation of a critical analysis of the terms “smart sustainable cities” and “smart sustainable islands” b the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors which concern the insular municipalities c the creation of an island’s smartification and sustainability index d the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

Sustainable Table | Welcome to Sustainable Table

Science.gov (United States)

Sustainable Seafood Industrial Agriculture Industrial Livestock Production Antibiotics Hormones rBGH Animal , safeguarding animal welfare and supporting local communities. Questions to Ask Asking questions is the best way Livestock Husbandry Sustainable Crop Production Innovative Agriculture New Farmers Organic Agriculture Local

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

Directory of Open Access Journals (Sweden)

Yun Wang

2018-03-01

Full Text Available MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII. The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Engineering Sustainability: A Technical Approach to Sustainability

OpenAIRE

Rosen, Marc A.

2012-01-01

Sustainability is a critically important goal for human activity and development. Sustainability in the area of engineering is of great importance to any plans for overall sustainability given 1) the pervasiveness of engineering activities in societies, 2) their importance in economic development and living standards, and 3) the significant impacts that engineering processes and systems have had, and continue to have, on the environment. Many factors that need to be considered and appropriate...

Making the Sustainable Development Goals Consistent with Sustainability

Directory of Open Access Journals (Sweden)

Mathis Wackernagel

2017-07-01

Full Text Available The UN’s Sustainable development Goals (SDGs are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”, and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

Making the Sustainable Development Goals Consistent with Sustainability

International Nuclear Information System (INIS)

Wackernagel, Mathis; Hanscom, Laurel; Lin, David

2017-01-01

The UN’s Sustainable development Goals (SDGs) are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”), and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

Making the Sustainable Development Goals Consistent with Sustainability

Energy Technology Data Exchange (ETDEWEB)

Wackernagel, Mathis, E-mail: mathis.wackernagel@footprintnetwork.org; Hanscom, Laurel; Lin, David [Global Footprint Network, Oakland, CA (United States)

2017-07-11

The UN’s Sustainable development Goals (SDGs) are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”), and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

Lysophosphatidic Acid Upregulates Laminin-332 Expression during A431 Cell Colony Dispersal

Directory of Open Access Journals (Sweden)

Hironobu Yamashita

2010-01-01

Full Text Available Lysophosphatidic acid (LPA is a bioactive phospholipid that affects various biological functions, such as cell proliferation, migration, survival, wound healing, and tumor invasion through LPA receptors. Previously, we reported that LPA induces A431 colony dispersal, accompanied by disruption of cell-cell contacts and cell migration. However, it remains unclear how LPA affects cell migration and gene expression during A431 colony dispersal. In this paper, we performed cDNA microarray analysis to investigate this question by comparing gene expression between untreated and LPA-treated A431 cells. Interestingly, these results revealed that LPA treatment upregulates several TGF-β1 target genes, including laminin-332 (Ln-332 components (α3, β3, and γ2 chains. Western blot analysis also showed that LPA increased phosphorylation of Smad2, an event that is carried out by TGF-β1 interactions. Among the genes upregulated, we further addressed the role of Ln-332. Real-time PCR analysis confirmed the transcriptional upregulation of all α3, β3, and γ2 chains of Ln-332 by LPA, corresponding to the protein level increases revealed by western blot. Further, the addition of anti-Ln-332 antibody prevented LPA-treated A431 colonies from dispersing. Taken together, our results suggest that LPA-induced Ln-332 plays a significant role in migration of individual cells from A431 colonies.

Sustainable Marketing

NARCIS (Netherlands)

Dam, van Y.K.

2017-01-01

In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

Sustainability and Organizational Change by Sustainable Crediting Therapy

Directory of Open Access Journals (Sweden)

Dragoş Ilie

2012-06-01

Full Text Available The objective of this paper is to demonstrate that one of the therapies to achieve sustainability and organizational change in the context of current challenges in the national economies is sustainable crediting. The research method is based on a survey of 30 commercial companies from various fields of activity that have or have not implemented, at the leadership level, the concept of sustainable crediting. The data collecting and processing approach has resulted in the determination of the main economic-financial indicators for a period of 5 years, indicators used by banks in relation with the credited organizations. The main results show that companies that have implemented the sustainable crediting concept are more able to achieve sustainability in their developed activity, as well as organizational change with positive effects on their business and on the company as a whole. The concept of sustainable crediting implies the capitalization of the commercial companies, the increase of the loan portfolio quality, the achievement of the financial balance and environmental protection

Upregulation of decorin by FXR in vascular smooth muscle cells

International Nuclear Information System (INIS)

He Fengtian; Zhang Qiuhong; Kuruba, Ramalinga; Gao Xiang; Li Jiang; Li Yong; Gong Wei; Jiang, Yu; Xie Wen; Li Song

2008-01-01

Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation

Sustainability in Business

DEFF Research Database (Denmark)

Tollin, Karin; Vej, Jesper

2012-01-01

How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level of market...... managers' mindsets, a framework addressing sustainability from four organisational learning schools was designed and followed......How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level...... of marketing. The central contribution of the typology is a strategic and managerial view on sustainability. Furthermore, the typology shows that sustainability in business is enacted from different areas of competences and fields in the literature (e.g. supply chain management, corporate branding, value...

The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.

Science.gov (United States)

Khan, Sumbul Jawed; Abidi, Syeda Nayab Fatima; Skinner, Andrea; Tian, Yuan; Smith-Bolton, Rachel K

2017-07-01

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.

Science.gov (United States)

Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismail; Tanguay, Jean-François; Calderone, Angelino

2015-05-15

Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. Copyright © 2015 the American Physiological Society.

Health and sustainability.

Science.gov (United States)

Kjӕrgård, Bente; Land, Birgit; Bransholm Pedersen, Kirsten

2014-09-01

In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the 'duality of structure' is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion and sustainability. Third, we use examples from agriculture and food production to illustrate that health and sustainability are mutually enabling and constraining. We conclude that while the renewed focus on food security and food inequalities has brought the health and sustainability dimensions of the food system onto the political agenda, the conceptualization of duality between health and sustainability could be a new platform for a critical and theoretical stance towards the market-oriented food system strategy. Thinking along the lines of duality means that the integration of health promotion strategies and sustainable development strategies cannot be based on an approach to integration in which either health or sustainability is given precedence over the other. From a duality perspective, integration means conceiving sustainability from a health perspective and health from a sustainability perspective. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Science.gov (United States)

Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

2016-04-01

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue.

Science.gov (United States)

Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, Bärbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

2011-11-01

Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in venous and lung tissue and to evaluate the underlying molecular mechanisms. C57Bl/6 mice underwent voluntary exercise or forced physical activity. Changes of vascular mRNA and protein levels and activity of eNOS, ecSOD and catalase were determined in aorta, heart, lung and vena cava. Both training protocols similarly increased relative heart weight and resulted in up-regulation of aortic and myocardial eNOS. In striking contrast, eNOS expression in vena cava and lung remained unchanged. Likewise, exercise up-regulated ecSOD in the aorta and in left ventricular tissue but remained unchanged in lung tissue. Catalase expression in lung tissue and vena cava of exercised mice exceeded that in aorta by 6.9- and 10-fold, respectively, suggesting a lack of stimulatory effects of hydrogen peroxide. In accordance, treatment of mice with the catalase inhibitor aminotriazole for 6 weeks resulted in significant up-regulation of eNOS and ecSOD in vena cava. These data suggest that physiological venous catalase activity prevents exercise-induced up-regulation of eNOS and ecSOD. Furthermore, therapeutic inhibition of vascular catalase might improve pulmonary rehabilitation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle.

Science.gov (United States)

Hussey, Sophie E; Lum, Helen; Alvarez, Andrea; Cipriani, Yolanda; Garduño-Garcia, Jesús; Anaya, Luis; Dube, John; Musi, Nicolas

2014-03-01

Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa Bα (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. A sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NFκB and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans. ClinicalTrials.gov NCT01740817.

Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease.

Science.gov (United States)

Koga, Hiroshi; Martinez-Vicente, Marta; Arias, Esperanza; Kaushik, Susmita; Sulzer, David; Cuervo, Ana Maria

2011-12-14

Autophagy contributes to the removal of prone-to-aggregate proteins, but in several instances these pathogenic proteins have been shown to interfere with autophagic activity. In the case of Huntington's disease (HD), a congenital neurodegenerative disorder resulting from mutation in the huntingtin protein, we have previously described that the mutant protein interferes with the ability of autophagic vacuoles to recognize cytosolic cargo. Growing evidence supports the existence of cross talk among autophagic pathways, suggesting the possibility of functional compensation when one of them is compromised. In this study, we have identified a compensatory upregulation of chaperone-mediated autophagy (CMA) in different cellular and mouse models of HD. Components of CMA, namely the lysosome-associated membrane protein type 2A (LAMP-2A) and lysosomal-hsc70, are markedly increased in HD models. The increase in LAMP-2A is achieved through both an increase in the stability of this protein at the lysosomal membrane and transcriptional upregulation of this splice variant of the lamp-2 gene. We propose that CMA activity increases in response to macroautophagic dysfunction in the early stages of HD, but that the efficiency of this compensatory mechanism may decrease with age and so contribute to cellular failure and the onset of pathological manifestations.

Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

International Nuclear Information System (INIS)

Rainio, Eeva-Marja; Ahlfors, Helena; Carter, Kara L.; Ruuska, Marja; Matikainen, Sampsa; Kieff, Elliott; Koskinen, Paeivi J.

2005-01-01

Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth

Survey on Impact of Public push on Sustainability marketing mix and Sustainability marketing mix on Sustainability marketing success

OpenAIRE

iman mousavian; bahram kheiry; vahidreza mirabi

2014-01-01

Partaking the movement in reaching a more sustainable planet, organizations should reconsider their marketing strategies according to the social and environmental impacts. Even though, attaining sustainability would become a serious challenge for them, but there exist no other options for the third millennium. The main purpose of this study is to investigate the Impact of public push on the sustainability marketing mix, as well as the effect of sustainability marketing mix on sustainability m...

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

Science.gov (United States)

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

From Sustainability-as-usual to Sustainability Excellence in Local Bioenergy Business

Directory of Open Access Journals (Sweden)

Heli Kasurinen

2017-06-01

Full Text Available Bioenergy business operators can significantly contribute to the sustainability of bioenergy systems. While research has addressed the maturity of corporate responsibility for sustainability, the maturity levels of bioenergy business have not been determined. The objectives of this research were to characterise the maturity levels of bioenergy corporate responsibility for sustainability and outline an approach by which companies can operate at the most mature sustainability excellence level. Literature, three workshops attended by bioenergy experts and a case study on biobutanol production in Brazil were used to develop the maturity model and approach. The results characterise the profitability, acceptability, and sustainability orientation maturity levels through sustainability questions and methods, and list the components of a systemic, holistic approach. Although the shift of business mindset from sustainability-as-usual to sustainability excellence is challenging, a systemic approach is necessary to broadly identify sustainability questions and a multitude of methods by which they can be answered.

Effect of age on upregulation of the cardiac adrenergic beta receptors

International Nuclear Information System (INIS)

Tumer, N.; Houck, W.T.; Roberts, J.

1990-01-01

Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors

Technology and sustainability

NARCIS (Netherlands)

Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

2011-01-01

In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

Sustainable NREL - Site Sustainability Plan FY 2015

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-01-01

NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

Sustainable Universities

DEFF Research Database (Denmark)

Grindsted, Thomas Skou

2011-01-01

Declarations on Sustainability in Higher Education (SHE) can be viewed as a piece of international regulation. Over the past 30 years research at universities has produced convincing data to warn about deterioration of the environment, resource scarcity and the need for sustainability. This in turn....... Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...

Myostatin signaling is up-regulated in female patients with advanced heart failure.

Science.gov (United States)

Ishida, Junichi; Konishi, Masaaki; Saitoh, Masakazu; Anker, Markus; Anker, Stefan D; Springer, Jochen

2017-07-01

Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients. Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis. Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (pmyostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients. In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

Prickly pear induces upregulation of liver LDL binding in familial heterozygous hypercholesterolemia

International Nuclear Information System (INIS)

Palumbo, B.; Palumbo, R.; Efthimiou, Y.; Stamatopoulos, J.; Sinzinger, H.; Oguogho, A.; Budinsky, A.; Sinzinger, H.

2003-01-01

The hypoglycemic effect of prickly pear is well known by native local Indian population since a long time. Beside the beneficial effects on lipid metabolism, oxidation injury and platelet function has been claimed in experimental animals. We recently found an upregulation of apo-B/E receptor. We therefore examined 10 patients with isolated heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run-in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly pear addition. Uptake of autologous 123 I-radiolabeled LDL was determined at entry as well as after 6 weeks of daily prickly pear ingestion. We found a significant (p 176.4 mg/dl; p 123 I-LDL binding by prickly pear in FH-patients in vivo and indicate that prickly pear exerts a significant hypolipidemic action via receptor upregulation. (author)

Fur and Sustainability

DEFF Research Database (Denmark)

Skjold, Else; Csaba, Fabian

2016-01-01

This paper explores the notion of deeper luxury, which insists that 'real' luxury should involve sustainable practices in the production and consumption of luxury goods. It traces historical and recent developments in the field of fur, to understand the implications, uncertainties and ambiguities...... of luxury’s confrontation with sustainability. Considering fur in relation to future standards for luxury products, we raise questions about moral problematisation and justification of luxury in terms of sustainability. We first examine the encounter of luxury with sustainability and explain...... the significance of the notion of ‘deeper luxury’. After taking stock of the impact of sustainability on luxury and various directions in which sustainable luxury is evolving, we discuss concepts of sustainable development in relation to the history of moral problematisation of luxury. This leads to the case...

No-Self, Natural Sustainability and Education for Sustainable Development

Science.gov (United States)

Wang, Chia-Ling

2017-01-01

This article explores the significance of sustainability and several ways in which education for sustainable development (ESD) can be considered. It presents several issues related to the theories of sustainability and ESD, which are generated based on a firm concept of anthropocentrism. ESD has been used for developing a scientific understanding…

Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

DEFF Research Database (Denmark)

Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

2014-01-01

Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

Conceptualizing Sustainably Produced Food for Promotional Purposes: A Sustainable Marketing Approach

Directory of Open Access Journals (Sweden)

Cecilia Solér

2012-03-01

Full Text Available Progress in transforming current food consumption and production practice in a sustainable direction is slow. Communicative, sustainable consumer policy instruments such as eco-labeling schemes have limited impact outside the green segment and within the mainstream market. This article asks how sustainably produced food can be described in order to promote such food. Based on six cases, it aims to conceptualize the common denominators of sustainable food production by drawing on recent literature on sustainable marketing and on food and sustainable development. Contradictions and implications in terms of labeling schemes, global sourcing and consumer food practice are discussed.

Short-term mastication after weaning upregulates GABAergic signalling and reduces dendritic spine in thalamus.

Science.gov (United States)

Ogawa, Mana; Nagai, Toshitada; Saito, Yoshikazu; Miyaguchi, Hitonari; Kumakura, Kei; Abe, Keiko; Asakura, Tomiko

2018-04-06

Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis. With respect to chemical synaptic transmission, glutamate decarboxylase and GABA receptors were upregulated in the chow diet group. The related genes, including vesicular GABA transporter, were also upregulated, suggesting that mastication activates GABAergic signalling. With respect to dendritic spine morphogenesis, Ingenuity Pathway Analysis predicted fewer extension of neurites and neurons and fewer number of branches in the chow diet group. The numbers of spines in the ventral posterolateral and posteromedial regions were significantly decreased. These results suggest that mastication in the early developing period upregulates GABAergic signalling genes, with a decrease of spines in the thalamus. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Using the Program Sustainability Assessment Tool to Assess and Plan for Sustainability

Science.gov (United States)

Mainor, Avia; Moreland-Russell, Sarah; Maier, Ryan C.; Brossart, Laura; Luke, Douglas A.

2014-01-01

Implementing and growing a public health program that benefits society takes considerable time and effort. To ensure that positive outcomes are maintained over time, program managers and stakeholders should plan and implement activities to build sustainability capacity within their programs. We describe a 3-part sustainability planning process that programs can follow to build their sustainability capacity. First, program staff and stakeholders take the Program Sustainability Assessment Tool to measure their program’s sustainability across 8 domains. Next, managers and stakeholders use results from the assessment to inform and prioritize sustainability action planning. Lastly, staff members implement the plan and keep track of progress toward their sustainability goals. Through this process, staff can more holistically address the internal and external challenges and pressures associated with sustaining a program. We include a case example of a chronic disease program that completed the Program Sustainability Assessment Tool and engaged in program sustainability planning. PMID:24456644

Sustainability Assessment Using a Unit-based Sustainability ...

African Journals Online (AJOL)

A sustainability assessment study was performed with three teaching departments at Rhodes University – Ichthyology and Fisheries Science, Anthropology, and Accounting. The assessment used a Unit-based Sustainability Assessment Tool (USAT) and was guided by systems thinking and the ontological framework ...

Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries

DEFF Research Database (Denmark)

Ahnstedt, Hilda; Cao, Lei; Krause, Diana N

2013-01-01

Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which...

Externality or sustainability economics?

International Nuclear Information System (INIS)

Bergh, Jeroen C.J.M. van den

2010-01-01

In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)

Hypoxia upregulates neutrophil degranulation and potential for tissue injury

Science.gov (United States)

Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

2016-01-01

Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

Local Sustainability

International Nuclear Information System (INIS)

Carrizosa Umana, Julio

1998-01-01

The current polemic about the possibilities of sustainable development has led to a renovated interest for the topic of the sustainability of the communities and the local sustainability. In front of the global sustainability whose conditions have been exposed by systemic ecologists and for macro economists, the sustainability of specific places arises in the planet whose conditions are object of study of the ecology of landscapes, of the ecological economy, of the cultural anthropology, of the environmental sociology and naturally, of the integral environmentalism. In this discussion the Colombian case charges unusual interest to be one of the few countries of Latin America, where a very dense net of municipalities exists, each one with its urban helmet and with a position and some functions defined by the political constitution of the nation. This net of municipalities and of urban helmets it also constitutes net of alternative to the current macro-cephalic situation. As well as Bogota grew, in a hundred years, of less than a hundred thousand inhabitants to six million inhabitants, each one of these municipalities contains a potential of growth that depends on the characteristics of its ecological, social, economic and politic sustainability

Afterschool Sustainability

Directory of Open Access Journals (Sweden)

Hilary D. Joyce

2014-12-01

Full Text Available Youth participation in quality extended learning opportunities (ELOs results in positive academic, physical, mental health, and social/emotional outcomes. Funding is essential to implementing and sustaining quality ELOs; however multiple funding barriers and challenges exist. Understanding the types of funds available for ELOs and the factors that influence sustainability is critical. Through surveys and telephone interviews of ELO providers, this descriptive study identified and examined ELO funding streams, the ways ELO providers use these funding streams, and the barriers and challenges to sustainability. ELO programs often relied on one major funding stream coupled with nutrition supports as well as in-kind resources. Barriers to sustainability included year-to-year funding, transportation costs, reducing community partnerships, and difficulty in diversifying funds. Recommendations to enhance ELO sustainability are offered, particularly in relation to overcoming the challenges to diversification of funding resources and establishing mutually supportive partnerships and collaboration.

Discovery of molecular mechanism of a clinical herbal formula upregulating serum HDL-c levels in treatment of metabolic syndrome by in vivo and computational studies.

Science.gov (United States)

Chen, Meimei; Yang, Fafu; Kang, Jie; Gan, Huijuan; Lai, Xinmei; Gao, Yuxing

2018-01-15

Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a famous clinical traditional Chinese medicine formula in Mets in China, which can obviously up-regulate serum HDL-c levels in Mets. However, till now, the molecular mechanism of up-regulation still remained unclear. In this study, an integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and molecular docking was developed to explore the molecular mechanism and chemical substance basis of WDD upregulating HDL-c levels. Compared with Mets model group, serum ABCA1 and HDL-c levels intervened by two different doses of WDD for two weeks were significantly up-regulated. Then, kohonen and LDA were applied to develop QSAR models for ABCA1 up-regulators based flavonoids. The derived QSAR model produced the overall accuracy of 100%, a very powerful tool for screening ABCA1 up-regulators. The QSAR model prediction revealed 67 flavonoids in WDD were ABCA1 up-regulators. Finally, they were subjected to the molecular docking to understand their roles in up-regulating ABCA1 expression, which led to discovery of 23 ABCA1 up-regulators targeting LXR beta. Overall, QSAR modeling and docking studies well accounted for the observed in vivo activities of ABCA1 affected by WDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

20-hydroxyecdysone upregulates Atg genes to induce autophagy in the Bombyx fat body

Science.gov (United States)

Tian, Ling; Ma, Li; Guo, Enen; Deng, Xiaojuan; Ma, Sanyuan; Xia, Qingyou; Cao, Yang; Li, Sheng

2013-01-01

Autophagy is finely regulated at multiple levels and plays crucial roles in development and disease. In the fat body of the silkworm, Bombyx mori, autophagy occurs and Atg gene expression peaks during the nonfeeding molting and pupation stages when the steroid hormone (20-hydroxyecdysone; 20E) is high. Injection of 20E into the feeding larvae upregulated Atg genes and reduced TORC1 activity resulting in autophagy induction in the fat body. Conversely, RNAi knockdown of the 20E receptor partner (USP) or targeted overexpression of a dominant negative mutant of the 20E receptor (EcRDN) in the larval fat body reduced autophagy and downregulated the Atg genes, confirming the importance of 20E-induction of Atg gene expression during pupation. Moreover, in vitro treatments of the larval fat body with 20E upregulated the Atg genes. Five Atg genes were potentially 20E primary-responsive, and a 20E response element was identified in the Atg1 (ortholog of human ULK1) promoter region. Furthermore, RNAi knockdown of 4 key genes (namely Br-C, E74, HR3 and βftz-F1) in the 20E-triggered transcriptional cascade reduced autophagy and downregulated Atg genes to different levels. Taken together, we conclude that in addition to blocking TORC1 activity for autophagosome initiation, 20E upregulates Atg genes to induce autophagy in the Bombyx fat body. PMID:23674061

Computational sustainability

CERN Document Server

Kersting, Kristian; Morik, Katharina

2016-01-01

The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

Triazophos up-regulated gene expression in the female brown planthopper, Nilaparvata lugens.

Science.gov (United States)

Bao, Yan-Yuan; Li, Bao-Ling; Liu, Zhao-Bu; Xue, Jian; Zhu, Zeng-Rong; Cheng, Jia-An; Zhang, Chuan-Xi

2010-09-01

The widespread use of insecticides has caused the resurgence of the brown planthopper, Nilaparvata lugens, in Asia. In this study, we investigated an organo-phosphorous insecticide, triazophos, and its ability to induce gene expression variation in female N. lugens nymphs just before emergence. By using the suppression subtractive hybridization method, a triazophos-induced cDNA library was constructed. In total, 402 differentially expressed cDNA clones were obtained. Real-time qPCR analysis confirmed that triazophos up-regulated the expression of six candidate genes at the transcript level in nymphs on day 3 of the 5th instar. These genes encode N. lugens vitellogenin, bystin, multidrug resistance protein (MRP), purine nucleoside phosphorylase (PNP), pyrroline-5-carboxylate reductase (P5CR) and carboxylesterase. Our results imply that the up-regulation of these genes may be involved in the induction of N. lugens female reproduction or resistance to insecticides.

Dynamic Sustainability. Sustainability Window Analysis of Chinese Poverty-Environment Nexus Development

Directory of Open Access Journals (Sweden)

Jyrki Luukkanen

2015-10-01

Full Text Available Sustainability Window is a new analysis tool for assessing the sustainability of development simultaneously in all of its three dimensions (environmental, economic, and social. The analysis method provides information of the maximum and minimum economic development that is required to maintain the direction of social and environmental development towards more sustainable targets. With the Sustainability Window method it is possible to easily analyze the sustainability using different indicators and different time periods making comparative analyses easy. The new method makes it also possible to analyze the dynamics of the sustainability and the changes over time in the width of the window. This provides a new perspective for analyzing the trends of sustainability and the impacts of underlying sustainability policies. As an illustration of the method, we have carried out an analysis of Chinese development using CO2 and SO2 emissions as indicators of the environmental dimension, number of non-poor people as an indicator of the social dimension and GDP as an indicator of the economic dimension.

Upregulation of FLG, LOR, and IVL Expression by Rhodiola crenulata Root Extract via Aryl Hydrocarbon Receptor: Differential Involvement of OVOL1

Directory of Open Access Journals (Sweden)

Akiko Hashimoto-Hachiya

2018-06-01

Full Text Available Rhodiola species are antioxidative, salubrious plants that are known to inhibit oxidative stress induced by ultraviolet and γ-radiation in epidermal keratinocytes. As certain phytochemicals activate aryl hydrocarbon receptors (AHR or OVO-like 1 (OVOL1 to upregulate the expression of epidermal barrier proteins such as filaggrin (FLG, loricrin (LOR, and involucrin (IVL, we investigated such regulation by Rhodiola crenulata root extract (RCE. We demonstrated that RCE induced FLG and LOR upregulation in an AHR-OVOL1-dependent fashion. However, RCE-mediated IVL upregulation was AHR-dependent but OVOL1-independent. Coordinated upregulation of skin barrier proteins by RCE via AHR may be beneficial in the management of barrier-disrupted inflammatory skin diseases such as atopic dermatitis.

Health and Sustainability

DEFF Research Database (Denmark)

Land, Birgit; Pedersen, Kirsten Bransholm; Kjærgård, Bente

2014-01-01

In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the ‘duality of structure’ is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering...... the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems...... or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion...

Sustainable Housing Design

DEFF Research Database (Denmark)

Lauring, Gert Michael

2016-01-01

Sustainable Housing Design. Integrating technical and housing quality aspects of sustainable architecture in civil engineering education. Summary An integrated design approach to sustainable architecture is outlined that combines concerns for zero energy building, good indoor climate and adequate...... phases. The outcome shows that integrated design further solutions where sustainable urban forms of settlement can be highly energy efficient while also attractive from a user perspective. Key words: Sustainable architecture, integrated design, zero-energy-housing, dense urban living. 1. Introduction...... When designing sustainable housing, energy optimization and satisfactory indoor climates are central issues that need to be incorporated from early design phases if to reach a coherent design. It might also be argued that the energy consumption of contemporary buildings only plays a rela-tively minor...

Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

Science.gov (United States)

Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

2011-06-15

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

Science.gov (United States)

Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

2015-08-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

Sustainable venture capital – catalyst for sustainable start-up success?

NARCIS (Netherlands)

Bocken, N.M.P.

2015-01-01

To address global sustainability challenges, major investments are required in sustainable businesses that deliver triple bottom line results. Although interest in sustainable businesses is on the rise, these businesses are not yet widespread. Venture capital investment has a key role to play in the

Factors Influencing Museum Sustainability and Indicators for Museum Sustainability Measurement

Directory of Open Access Journals (Sweden)

Izabela Luiza Pop

2016-01-01

Full Text Available The purpose of this research was to identify the factors upon which museum sustainability depends and the way in which this can be measured. Methodologically, we applied a qualitative research approach, using semi-structured interviews with experts from the Romanian museum sector, complemented by an in-depth study of the literature in this field. Results indicated that any objective measuring of sustainability must take into account the size of a museum’s collections and its organizational structure. It was also found that museum type can affect sustainability via its competitive advantage. However, the sustainability of a museum is not strictly determined by these factors, but also by the management and marketing strategies applied. Based on analysis of literature- and respondent-based factors influencing sustainability, this article proposes a set of 33 indicators that can be used by museums to measure their sustainability, as well as a model that enables evaluation of the sustainability levels of various museums comparatively, regardless of their type, size or importance (e.g., national, regional and local. The results obtained are useful both from a theoretical point of view, given that there are few writings on this topic, and from a practical point of view, as they provide a basis for a clear, objective model of museum sustainability measurement.

Gene up-regulation in response to predator kairomones in the water flea, Daphnia pulex

Directory of Open Access Journals (Sweden)

Okada Yasukazu

2010-04-01

Full Text Available Abstract Background Numerous cases of predator-induced polyphenisms, in which alternate phenotypes are produced in response to extrinsic stimuli, have been reported in aquatic taxa to date. The genus Daphnia (Branchiopoda, Cladocera provides a model experimental system for the study of the developmental mechanisms and evolutionary processes associated with predator-induced polyphenisms. In D. pulex, juveniles form neckteeth in response to predatory kairomones released by Chaoborus larvae (Insecta, Diptera. Results Previous studies suggest that the timing of the sensitivity to kairomones in D. pulex can generally be divided into the embryonic and postembryonic developmental periods. We therefore examined which of the genes in the embryonic and first-instar juvenile stages exhibit different expression levels in the presence or absence of predator kairomones. Employing a candidate gene approach and identifying differentially-expressed genes revealed that the morphogenetic factors, Hox3, extradenticle and escargot, were up-regulated by kairomones in the postembryonic stage and may potentially be responsible for defense morph formation. In addition, the juvenile hormone pathway genes, JHAMT and Met, and the insulin signaling pathway genes, InR and IRS-1, were up-regulated in the first-instar stage. It is well known that these hormonal pathways are involved in physiological regulation following morphogenesis in many insect species. During the embryonic stage when morphotypes were determined, one of the novel genes identified by differential display was up-regulated, suggesting that this gene may be related to morphotype determination. Biological functions of the up-regulated genes are discussed in the context of defense morph formation. Conclusions It is suggested that, following the reception of kairomone signals, the identified genes are involved in a series of defensive phenotypic alterations and the production of a defensive phenotype.

Reactive or proactive approach towards sustainability? A conceptual framework based on sustainable business models to increase stakeholders' sustainable value capture

DEFF Research Database (Denmark)

Rosati, Francesco; Morioka, Sandra; Monteiro de Carvalho, Marly

2016-01-01

and challenging companies to seek for business opportunities with an entrepreneurial attitude to help solving sustainable development challenges. By combining both approaches, organizations have the opportunity to increase sustainable value capture by its stakeholders, acting on their institutional responsibility...... as instrument to help companies describe, analyze, manage and communicate their sustainable value proposition, creation, delivery and capture mechanism. In particular, this research focuses on value capture dynamics, aiming to explore how companies can increase their contribution to sustainable development...... sustainability. In this sense, a proactive approach to foster sustainable value capture can complement the reactive approach by delivering value beyond stakeholders' expectations. In this case, companies use their capabilities to identify opportunities to create and deliver sustainable value that stakeholders...

Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

International Nuclear Information System (INIS)

Sanità, Patrizia; Capulli, Mattia; Teti, Anna; Galatioto, Giuseppe Paradiso; Vicentini, Carlo; Chiarugi, Paola; Bologna, Mauro; Angelucci, Adriano

2014-01-01

Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive

Sustainable Transportation

DEFF Research Database (Denmark)

Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

2014-01-01

The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

Linking Complexity and Sustainability Theories: Implications for Modeling Sustainability Transitions

Directory of Open Access Journals (Sweden)

Camaren Peter

2014-03-01

Full Text Available In this paper, we deploy a complexity theory as the foundation for integration of different theoretical approaches to sustainability and develop a rationale for a complexity-based framework for modeling transitions to sustainability. We propose a framework based on a comparison of complex systems’ properties that characterize the different theories that deal with transitions to sustainability. We argue that adopting a complexity theory based approach for modeling transitions requires going beyond deterministic frameworks; by adopting a probabilistic, integrative, inclusive and adaptive approach that can support transitions. We also illustrate how this complexity-based modeling framework can be implemented; i.e., how it can be used to select modeling techniques that address particular properties of complex systems that we need to understand in order to model transitions to sustainability. In doing so, we establish a complexity-based approach towards modeling sustainability transitions that caters for the broad range of complex systems’ properties that are required to model transitions to sustainability.

Sustainable Concrete Technology

Directory of Open Access Journals (Sweden)

Sim J.

2015-12-01

Full Text Available The growing concern over global warming and significant ecological changes requires sustainable development in all fields of science and technology. Concrete not only consumes huge amount of energy and natural sources, but also emits large amount of CO2, mainly due to the production of cement. It is evident that such large amount of concrete production has put significant impact on the energy, resource, environment, and ecology of the society. Hence, how to develop the concrete technology in a sustainable way has become a significant issue. In this paper, some of Korean researches for sustainable development of concrete are presented. These are sustainable strengthening for deteriorated concrete structure, sustainable reinforcement of new concrete structure, sustainable concrete using recycled aggregate and supplementary cementing materials and finally application of each technique to precast concrete.

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.

Science.gov (United States)

Shamseddine, A A; Clarke, C J; Carroll, B; Airola, M V; Mohammed, S; Rella, A; Obeid, L M; Hannun, Y A

2015-10-29

Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

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Rui-Xin Yang

2017-06-01

Full Text Available Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB, against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

Science.gov (United States)

Yang, Rui-Xin; Lei, Jie; Wang, Bo-Dong; Feng, Da-Yun; Huang, Lu; Li, Yu-Qian; Li, Tao; Zhu, Gang; Li, Chen; Lu, Fang-Fang; Nie, Tie-Jian; Gao, Guo-Dong; Gao, Li

2017-01-01

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro . SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Sustainable clothing: challenges, barriers and interventions for encouraging more sustainable consumer behaviour

OpenAIRE

Harris, Fiona; Roby, Helen; Dibb, Sally

2016-01-01

Research with consumers has revealed limited awareness of the sustainability impact of clothing (Goworek et al., 2012). Semi-structured interviews conducted with a range of experts in sustainable clothing to increase understanding of the challenges for sustainable clothing revealed that a focus on sustainability alone will not drive the necessary changes in consumers’ clothing purchase, care and disposal behaviour for three reasons: (i) clothing sustainability is too complex; (ii) consumers a...

Is Sustainable Remediation Now a Self-Sustaining Process? an International Progress Report

Science.gov (United States)

Smith, J. W. N.

2014-12-01

Sustainable remediation - the consideration of environmental, social and economic factors associated with soil and groundwater risk-management options, to help select the best overall solution - has been a rapidly evolving topic in recent years. The first published reference[1] to 'sustainable remediation' was in the title of a 1999 conference paper by Kearney et al., (1999), but activity really accelerated in the middle-late 2000's, with establishment of a number of collaborative sustainable remediation groups and fora, and increased publication rates in the peer reviewed literature (Fig 1). Figure 1. Journal paper publications with search term 'sustainable remediation' (SCOPUS survey, 17 July 2014) This presentation will review the international progress of sustainable remediation concept development and application in regulatory and corporate decision-making processes. It will look back at what has already been achieved, provide an update on the latest initiatives and developments, and look forward to what the future of sustainable remediation might look like. Specifically it will describe: Sustainable remediation frameworks: synergies and international collaboration; Latest guidance and tools developed by the various sustainable remediation organisations (SuRFs), including the SuRF-UK Best Management Practices and Tier 1 Briefcase; Best practice standard development by ASTM and ISO; Regulatory acceptance of sustainable remediation, including incorporation into legislation, and the NICOLE - Common Forum Joint statement on 'risk-informed and sustainable remediation' in Europe; Examples of corporate adoption of sustainable remediation principles. The presentation will conclude with a look forward to a vision of sustainable remediation in 2020.

Sustained-Paced Finger Tapping: A Novel Approach to Measure Internal Sustained Attention

Directory of Open Access Journals (Sweden)

Marco A. Petilli

2018-05-01

Full Text Available Sustained attention is a fundamental prerequisite for all cognitive functions and its impairment is a common aftermath of both developmental and acquired neurological disorders. To date, all the sustained attention tasks rely heavily on selective attention to external stimuli. The interaction between selective and sustained attention represents a limit in the field of assessment and may mislead researchers or distort conclusions. The aim of the present perspective study was to propose a sustained version of the Paced Finger Tapping (S-PFT test as a novel approach to measure sustained attention that does not leverage external stimuli. Here, we administered S-PFT and other attentional tasks (visual sustained attention, visuospatial attention capacity, selective attention, and divided attention tasks to 85 adolescents. Thus, we provide evidence suggesting that S-PFT is effective in causing performance decrement over time, an important trademark of sustained attention tasks. We also present descriptive statistics showing the relationship between S-PFT and the other attentional tasks. These analyses show that, unlike visual sustained attention tests, performances to our task of internal sustained attention were not correlated to measures of selective attention and visuospatial attention capacity. Our results suggest that S-PFT could represent a promising and alternative tool both for empirical research and clinical assessment of sustained attention.

Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

Science.gov (United States)

Shaw, Jillian L; Chang, Karen T

2013-01-01

Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

LCA and Sustainability

DEFF Research Database (Denmark)

Moltesen, Andreas; Bjørn, Anders

2018-01-01

LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report...... is then demonstrated, and the strategy of LCA to achieving environmental protection, namely to guide the reduction of environmental impacts per delivery of a function, is explained. The attempt to broaden the scope of LCA, beyond environmental protection, by so-called life cycle sustainability assessment (LCSA......) is outlined. Finally, the limitations of LCA in guiding a sustainable development are discussed....

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

Science.gov (United States)

Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

Directory of Open Access Journals (Sweden)

Bin Hong

2012-06-01

Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

Gemfibrozil, a lipid-lowering drug, upregulates interleukin-1 receptor antagonist in mouse cortical neurons: Implications for neuronal self-defense

Science.gov (United States)

Corbett, Grant T.; Roy, Avik; Pahan, Kalipada

2012-01-01

Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, interleukin-1 beta (IL-1β), a proinflammatory cytokine, is implicated in the pathogenesis of neurodegenerative diseases. While IL-1β binds to its high-affinity receptor, interleukin-1 receptor (IL-1R), and upregulates proinflammatory signaling pathways, interleukin-1 receptor antagonist (IL-1Ra) adheres to the same receptor and inhibits proinflammatory cell signaling. Therefore, upregulation of IL-1Ra is considered important in attenuating inflammation. The present study underlines a novel application of gemfibrozil, an FDA-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gemfibrozil alone induced an early and pronounced increase in the expression of IL-1Ra in primary mouse cortical neurons. Activation of type IA p110α phosphatidylinositol 3-kinase (PI3-K) and Akt by gemfibrozil and abrogation of gemfibrozil-induced upregulation of IL-1Ra by inhibitors of PI3-K and Akt indicate a role of the PI3-K – Akt pathway in the upregulation of IL-1Ra. Gemfibrozil also induced the activation of cAMP response element-binding (CREB) via the PI3-K – Akt pathway and siRNA attenuation of CREB abolished the gemfibrozil-mediated increase in IL-1Ra. Furthermore, gemfibrozil was able to protect neurons from IL-1β insult. However, siRNA knockdown of neuronal IL-1Ra abrogated the protective effect of gemfibrozil against IL-1β suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Together, these results highlight the importance of the PI3-K – Akt – CREB pathway in mediating gemfibrozil-induced upregulation of IL-1Ra in neurons and suggest gemfibrozil as a possible therapeutic treatment for propagating neuronal self defense in neuroinflammatory and neurodegenerative disorders. PMID:22706077

Toward sustainable logistics

NARCIS (Netherlands)

Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

2017-01-01

The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

Toward sustainable logistics

NARCIS (Netherlands)

Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

2018-01-01

The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

Moving Towards Sustainable Food Consumption : Identifying Barriers to Sustainable Student Diets

OpenAIRE

Ede, James; Graine, Sophia; Rhodes, Chris

2011-01-01

Adopting more sustainable consumption habits has been identified as a necessary step in the progression towards a sustainable society. In the area of sustainable consumption, personal food behaviour represents a strong leverage point. University students have been identified as a strategic audience; habits established during this transformative period can track forward into later life. This study seeks to identify the barriers inhibiting students from eating more sustainably. Perceived benefi...

Annual Sustainability Report FY 2014. Incorporates NREL Site Sustainability Plan

Energy Technology Data Exchange (ETDEWEB)

Rukavina, Frank [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-07-01

NREL's Sustainability Program is responsible for upholding all executive orders, federal regulations, U.S. Department of Energy (DOE) orders, and goals related to sustainable and resilient facility operations. But NREL continues to expand sustainable practices above and beyond the laboratory's regulations and requirements to ensure that the laboratory fulfills its mission into the future, leaves the smallest possible legacy footprint, and models sustainable operations and behaviors on national, regional, and local levels. The report, per the GRI reporting format, elaborates on multi-year goals relative to executive orders, achievements, and challenges; and success stories provide specific examples. A section called 'Sustaining NREL's Future Through Integration' provides insight into how NREL is successfully expanding the adoption of renewable energy technologies through integration.

Neighborhood Sustainability Assessment: Evaluating Residential Development Sustainability in a Developing Country Context

Directory of Open Access Journals (Sweden)

Tan Yigitcanlar

2015-03-01

Full Text Available Rapid urbanization, improved quality of life, and diversified lifestyle options have collectively led to an escalation in housing demand in our cities, where residential areas, as the largest portion of urban land use type, play a critical role in the formation of sustainable cities. To date there has been limited research to ascertain residential development layouts that provide a more sustainable urban outcome. This paper aims to evaluate and compare sustainability levels of residential types by focusing on their layouts. The paper scrutinizes three different development types in a developing country context—i.e., subdivision, piecemeal, and master-planned developments. This study develops a “Neighborhood Sustainability Assessment” tool and applies it to compare their sustainability levels in Ipoh, Malaysia. The analysis finds that the master-planned development, amongst the investigated case studies, possesses the potential to produce higher levels of sustainability outcomes. The results reveal insights and evidence for policymakers, planners, development agencies and researchers; advocate further studies on neighborhood-level sustainability analysis, and; emphasize the need for collective efforts and an effective process in achieving neighborhood sustainability and sustainable city formation.

Wrapping Our Brains around Sustainability

Directory of Open Access Journals (Sweden)

Mary Ann Curran

2009-03-01

Full Text Available As many of us begin to embrace the concept of sustainability, we realize that it is not simply something that we ‘do.’ Rather, sustainability is a destination that we aspire to reach with the selection of the sustainable pathways that we choose as we proceed along the journey. We are embarking on a new journey with the creation of Sustainability, an on-line, open access journal. As stated on the journal’s website, Sustainability is an international and cross-disciplinary scholarly journal of environmental, cultural, economic and social sustainability of human beings, which provides an advanced forum for studies that are related to sustainability and sustainable development. To genuinely wrap our brains around the impact that our actions have on the sustainability of our planet, we must first understand something of the big picture and have a firm grasp of the terminology. To help further clarify the elusive term ‘sustainability,’ without attempting to provide an exact definition, this paper outlines various, inter-related concepts and basic practices and approaches that are being used in the name of sustainability, including: traditional end-of-pipe control strategies, life cycle, environmental sustainability, urban sustainability, industrial ecology, business sustainability, sustainable supply chain systems, sustainability indicators and metrics, green chemistry and green engineering, design for the environment, sustainable buildings, eco-tourism, and renewable and sustainable energy and fuels.

Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.

Directory of Open Access Journals (Sweden)

Zhaoming Li

Full Text Available Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.

Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production.

Science.gov (United States)

Brégnard, Christelle; Guerra, Jessica; Déjardin, Stéphanie; Passalacqua, Frank; Benkirane, Monsef; Laguette, Nadine

2016-06-01

Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4(FANCP) deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

DEFF Research Database (Denmark)

Sørensen, Karen Marie Juul; Meldgaard, Theresa; Melchjorsen, Connie Jenning

2017-01-01

BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection...... of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure....... RESULTS: We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined...

Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)(n) Repeats by PNA or LNA Targeting

DEFF Research Database (Denmark)

Bergquist, Helen; Rocha, Cristina S. J.; Alvarez-Asencio, Ruben

2016-01-01

Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich’s ataxia. (GAA)n expansions form non-canonical structures, including intramolecular triplex (H-DNA), and R-loops and are associated with epigen...

Sustainable Learning Organizations

Science.gov (United States)

Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

2011-01-01

Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

Handbook of sustainable engineering

CERN Document Server

Lee, Kun-Mo

2013-01-01

"The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

Sustainable collaboration : The impact of governance and institutions on sustainable performance

NARCIS (Netherlands)

Niesten, Eva; Jolink, Albert; Lopes de Sousa Jabbour, Ana Beatriz; Chappin, Maryse; Lozano, Rodrigo

2017-01-01

Collaboration between firms is important to stimulate the transition to a more sustainable society. This special volume shows that collaboration is indeed one of the preferred forms of governance to manage relations between firms in a sustainability context. Collaboration enhances sustainable

Sustainability and Entrepreneurial Action

DEFF Research Database (Denmark)

Korsgaard, Steffen T.; Anderson, Alistair

Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...... entrepreneurship - which uses bricolage in various ways to create sustainable solutions. Implications and value - The concept of resource oriented sustainable entrepreneurship contributes to the theoretical understanding of how entrepreneurial action can support sustainability, Furthermore the case study has...

Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

International Nuclear Information System (INIS)

Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

2013-01-01

Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

Sustainable consumption

DEFF Research Database (Denmark)

Prothero, Andrea; Dobscha, Susan; Freund, Jim

2011-01-01

This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

Sustainable Consumption

DEFF Research Database (Denmark)

Røpke, Inge

2015-01-01

The intention of this chapter is to explore the role of consumption and consumers in relation to sustainability transition processes and wider systemic transformations. In contrast to the individualistic focus in much research on sustainable consumption, the embeddedness of consumption activities...... in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...

Sustainable transformation

DEFF Research Database (Denmark)

Andersen, Nicolai Bo

This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt......, that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

Interpreting sustainable development

Institute of Scientific and Technical Information of China (English)

1998-01-01

Over the past decade, the term" sustainable development"has emerged as the principal concept in the development field. The concept emerged in the 1970s and was first promoted in the international environmental and development communities with the publication of the " world conservation strategy"(1980). It was popularized by the Brundtland report, " Our common future"(1987). The Brundtland Commission defined sustainable development as " development which meets the needs of the present, without compromising the sustainability of future generation to meet their own needs". The Earth Summit(1992) established "sustainable development" as the most important policy of the 21st century. Since then, the relationship between development and environment has been widely discussed and sustainabale development is now an important part of the vocabulary of environmental policy research and analysis. In this paper, we begin by tracing the evolution of the concept of sustainable development. Definitions of sustainable development in ecology, economics and sociology are then explored and discussed. This paper also examine the contribution that a broadly-based concept of sustainable development can make: as a goal, an attitude and as a guiding principle for integrating economic development and environmental protection.

Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids

Directory of Open Access Journals (Sweden)

M. Grazia Cotticelli

2013-01-01

Full Text Available Friedreich ataxia is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, dysarthria, areflexia, sensory loss, skeletal deformities, and hypertrophic cardiomyopathy. Most disease alleles have a trinucleotide repeat expansion in the first intron of the FXN gene, which decreases expression of the encoded protein frataxin. Frataxin is involved in iron–sulfur-cluster (ISC assembly in the mitochondrial matrix, and decreased frataxin is associated with ISC-enzyme and mitochondrial dysfunction, mitochondrial iron accumulation, and increased oxidative stress. To assess the role of oxidative stress in lipid peroxidation in Friedreich ataxia we used the novel approach of treating Friedreich ataxia cell models with polyunsaturated fatty acids (PUFAs deuterated at bis-allylic sites. In ROS-driven oxidation of PUFAs, the rate-limiting step is hydrogen abstraction from a bis-allylic site; isotopic reinforcement (deuteration of bis-allylic sites slows down their peroxidation. We show that linoleic and α-linolenic acids deuterated at the peroxidation-prone bis-allylic positions actively rescue oxidative-stress-challenged Friedreich ataxia cells. The protective effect of the deuterated PUFAs is additive in our models with the protective effect of the CoQ10 analog idebenone, which is thought to decrease the production of free radicals. Moreover, the administration of deuterated PUFAs resulted in decreased lipid peroxidation as measured by the fluorescence of the fatty acid analog C11-BODIPY (581/591 probe. Our results are consistent with a role for lipid peroxidation in Friedreich ataxia pathology, and suggest that the novel approach of oral delivery of isotope-reinforced PUFAs may have therapeutic potential in Friedreich ataxia and other disorders involving oxidative stress and lipid peroxidation.

Sustainable consumption and marketing

NARCIS (Netherlands)

Dam, van Y.K.

2016-01-01

Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

Sustainability and Risk Disclosure: An Exploratory Study on Sustainability Reports

Directory of Open Access Journals (Sweden)

Elisa Truant

2017-04-01

Full Text Available Recent policy changes in sustainability reporting, such as the ones related to the new European Directive on non-financial disclosure (2014/95/EU, the standards issued by the American Sustainability Accounting Standard Board (SASB, the G4 guidelines issued by the Global Sustainability Standard Board (GSSB, and the framework of the International Integrated Reporting Council (IIRC stress the importance of extending the disclosure of ethical, social, and environmental risks within financial and social-environmental reporting. Institutional pressure has notably increased among organizations, in setting up risk management tools to understand sustainability risks within managerial and reporting practices. Given such institutional pressure, the corporate reaction in providing additional sustainability risk disclosure calls for attention and scrutiny. Therefore, this study aims at addressing such issues from an exploratory perspective. We based our analysis on a sample of large Italian organizations that issued sustainability disclosure in accordance with the Global Reporting Initiative (GRI, G4 guidelines, and we tested the relationship between their level of risk disclosure and other relevant variables. Consistently with the literature, we found that “experienced” sustainable reporters provide a significant volume of disclosure, and that disclosure quality on risk is positively influenced by their international presence and reporting experience. However, when accounting for specific risk-related areas of disclosure, only a few of them seem to adopt a managerial perspective linking strategy, risk metrics, and disclosure.

Sustainable Business Models - A Need For New And Sustainable Business Models

OpenAIRE

Heir, Nina

2016-01-01

Business plays a key role for the sustainable development of the society. However, business models of today do not have a sustainable perspective, indicating that they do not balance the three dimensions of sustainability; the social, environmental and economical dimension. A change at the business model level is therefore required for sustainable business models to become the new business models of tomorrow. The purpose of this study is to increase the knowledge of how companies can con...

Practical appraisal of sustainable development-Methodologies for sustainability measurement at settlement level

International Nuclear Information System (INIS)

Moles, Richard; Foley, Walter; Morrissey, John; O'Regan, Bernadette

2008-01-01

This paper investigates the relationships between settlement size, functionality, geographic location and sustainable development. Analysis was carried out on a sample of 79 Irish settlements, located in three regional clusters. Two methods were selected to model the level of sustainability achieved in settlements, namely, Metabolism Accounting and Modelling of Material and Energy Flows (MA) and Sustainable Development Index Modelling. MA is a systematic assessment of the flows and stocks of material within a system defined in space and time. The metabolism of most settlements is essentially linear, with resources flowing through the urban system. The objective of this research on material and energy flows was to provide information that might aid in the development of a more circular pattern of urban metabolism, vital to sustainable development. In addition to MA, a set of forty indicators were identified and developed. These target important aspects of sustainable development: transport, environmental quality, equity and quality of life issues. Sustainability indices were derived through aggregation of indicators to measure dimensions of sustainable development. Similar relationships between settlement attributes and sustainability were found following both methods, and these were subsequently integrated to provide a single measure. Analysis identified those attributes of settlements preventing, impeding or promoting progress towards sustainability

Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

Directory of Open Access Journals (Sweden)

Jillian L Shaw

Full Text Available Post-mortem brains from Down syndrome (DS and Alzheimer's disease (AD patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1, but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP, which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

Sustainability Marketing Commitment

DEFF Research Database (Denmark)

Tollin, Karin; Bech Christensen, Lars

2017-01-01

sustainability in marketing, processes associated with sustainability marketing commitment, drivers of sustainability marketing at the functional level of marketing, and its organizational context. Using survey data from 269 managers in marketing, covering a broad range of industries in Sweden and Denmark, we...... took a structural modelling approach to examine construct relationships, mediation, and moderation effects. Overall, the findings show that marketing capabilities associated with the innovation of new products, services, and business models constitute a strong driver to leverage sustainability......Corporate sustainability is an important strategy and value orientation for marketing, but scarce research addresses the organizational drivers and barriers to including it in companies’ marketing strategies and processes. The purpose of this study is to determine levels of commitment to corporate...

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

Science.gov (United States)

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Zhen-Bo [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China); Shen, Xun, E-mail: shenxun@sun5.ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China)

2009-09-04

To know if thioredoxin reductase 1 (TrxR1) plays a role in antioxidant defense mechanisms against atherosclerosis, effect of TrxR1 on expression/release of monocyte chemoattractant protein (MCP-1) was investigated in activated human endothelial-like EAhy926 cells. The MCP-1 release and expression, cellular generation of reactive oxygen species (ROS), nuclear translocation and DNA-binding activity of NF-{kappa}B subunit p65 were assayed in cells either overexpressing recombinant TrxR1 or having their endogenous TrxR1 knocked down. It was found that overexpression of TrxR1 enhanced, while knockdown of TrxR1 reduced MCP-1 release and expression. Upregulation of MCP-1 by TrxR1 was associated with increasing generation of intracellular ROS generation, enhanced nuclear translocation and DNA-binding activity of NF-{kappa}B. Assay using NF-{kappa}B reporter revealed that TrxR1 upregulated transcriptional activity of NF-{kappa}B. This study suggests that TrxR1 enhances ROS generation, NF-{kappa}B activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque.

Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

Energy Technology Data Exchange (ETDEWEB)

Su, Cunjin; Shi, Aiming; Cao, Guowen [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Tao, Tao [Department of Urology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009 (China); Chen, Ruidong [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Zhanhong; Shen, Zhu; Tao, Hong; Cao, Bin [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Duanmin, E-mail: hudmsdfey@sina.com [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Bao, Junjie, E-mail: baojjsdfey@sina.com [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)

2015-05-15

There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNA to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.

PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

International Nuclear Information System (INIS)

Kan-o, Keiko; Matsumoto, Koichiro; Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi; Inoue, Hiromasa

2013-01-01

Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB

N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells.

Science.gov (United States)

Liu, Yanli; Yang, Fen; Liang, Shengying; Liu, Qing; Fu, Sulei; Wang, Zhenyu; Yang, Ciqing; Lin, Juntang

2018-01-01

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

The Sustainability Cone - A holistic framework to integrate sustainability thinking into manufacturing

DEFF Research Database (Denmark)

Rödger, Jan-Markus; Bey, Niki; Alting, Leo

2016-01-01

Integrating sustainability into manufacturing is a multifaceted endeavour. Global sustainability aspects and specific manufacturing success factors have to be combined with life cycle thinking in order to get the holistic view on manufacturing which is needed to make truly sustainability-oriented......Integrating sustainability into manufacturing is a multifaceted endeavour. Global sustainability aspects and specific manufacturing success factors have to be combined with life cycle thinking in order to get the holistic view on manufacturing which is needed to make truly sustainability...... - as the missing link which closes these gaps by providing necessary holistic and consistent overview while being aligned with established stage-gate project execution models, thus ensuring practical applicability as shown for a highly automated production cell. The paper shows how to apply life cycle target...

FORUM: Is Ecotourism Sustainable?

Science.gov (United States)

Wall

1997-07-01

/ It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

Sustainable Cities

DEFF Research Database (Denmark)

Georg, Susse; Garza de Linde, Gabriela Lucía

Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

Sustainable wireless networks

CERN Document Server

Zheng, Zhongming; Xuemin

2013-01-01

This brief focuses on network planning and resource allocation by jointly considering cost and energy sustainability in wireless networks with sustainable energy. The characteristics of green energy and investigating existing energy-efficient green approaches for wireless networks with sustainable energy is covered in the first part of this brief. The book then addresses the random availability and capacity of the energy supply. The authors explore how to maximize the energy sustainability of the network and minimize the failure probability that the mesh access points (APs) could deplete their

Culture in Sustainability--Defining Cultural Sustainability in Education

Science.gov (United States)

Laine, Marja

2016-01-01

The definition of cultural sustainability in education is explored in this article by looking into conceptions of cultural sustainability collected through expert queries and focus group engagement. These conceptions are compared with the scientific and especially pedagogical discourse on the matter as well as Soini and Birkeland's theory of story…

DNA triplex structures in neurodegenerative disorder, Friedreich's ...

Indian Academy of Sciences (India)

2012-06-25

Jun 25, 2012 ... clearly suggests that the shape of DNA is the determining factor in the cellular function. FRDA is the only ..... SCA VII. CAG. 4–35. 28–35. 37 –200. SBMA. CAG. 15–31. –. 40–62 ... production of Frataxin (Babcock et al. 1997).

Sustainability and uncertainty

DEFF Research Database (Denmark)

Jensen, Karsten Klint

2007-01-01

The widely used concept of sustainability is seldom precisely defined, and its clarification involves making up one's mind about a range of difficult questions. One line of research (bottom-up) takes sustaining a system over time as its starting point and then infers prescriptions from...... this requirement. Another line (top-down) takes an economical interpretation of the Brundtland Commission's suggestion that the present generation's needsatisfaction should not compromise the need-satisfaction of future generations as its starting point. It then measures sustainability at the level of society...... a clarified ethical goal, disagreements can arise. At present we do not know what substitutions will be possible in the future. This uncertainty clearly affects the prescriptions that follow from the measure of sustainability. Consequently, decisions about how to make future agriculture sustainable...

Education for sustainable development

DEFF Research Database (Denmark)

Breiting, Søren

2009-01-01

 An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related ...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....... An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...

Sustainable housing as part of sustainable development - visions and experiences from Denmark

DEFF Research Database (Denmark)

Jørgensen, Michael Søgaard

2010-01-01

The paper discusses different approaches to sustainable development with main focus on sustainable housing, but also local climate activities with focus on transportation, food and local businesses are discussed. The focus in the paper is mainly on experiences from Denmark. The paper starts out...... with a short introduction to theoretical approaches to analyses of sustainable housing and other sustainability initiatives as innovation processes. Afterwards some social and political characteristics of Denmark are presented and one of the recent sustainability initiatives in Denmark, the climate plan from...... the Danish Society of Engineers is described. The second part of the paper discusses Danish sustainable housing strategies focusing on new houses and refurbishment of existing houses. Finally some recent experiences from a local climate cooperation between a technical university, a municipal administration...

The Globe Sustained: Shakespeare’s allegory for sustainable development

NARCIS (Netherlands)

Casteren van Cattenburch, Iris

2017-01-01

Sustainability theory shows that the sustainability problem is a value orientation problem. In a recent study, Klaas van Egmond identified an underlying pattern of a crossed circle, representing affirmative and adversative value orientations, whose disintegration engenders unsustainable tendencies.

Sustainability and Risk Disclosure: An Exploratory Study on Sustainability Reports

OpenAIRE

Elisa Truant; Laura Corazza; Simone Domenico Scagnelli

2017-01-01

Recent policy changes in sustainability reporting, such as the ones related to the new European Directive on non-financial disclosure (2014/95/EU), the standards issued by the American Sustainability Accounting Standard Board (SASB), the G4 guidelines issued by the Global Sustainability Standard Board (GSSB), and the framework of the International Integrated Reporting Council (IIRC) stress the importance of extending the disclosure of ethical, social, and environmental risks within financial ...

Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

Directory of Open Access Journals (Sweden)

Ana Paula Santin Bertoni

2015-01-01

Full Text Available Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P<0.0001; 2.39 times, P=0.01; 1.58 times, P=0.0003; and 1.87 times, P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P<0.0001; 1.75 times, P=0.037; and 1.95 times, P<0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P=0.069. These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

Stabilizing Sustainability

DEFF Research Database (Denmark)

Reitan Andersen, Kirsti

The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

The sustainable development

International Nuclear Information System (INIS)

2004-01-01

In the framework of the sustainable development week (june 2003), Actu Environnement published a complete document on the sustainable development to inform the public, recall the main steps of this notion (Rio conference and the following conferences) and the possible employments. It presents also the main organizations acting in the sustainable development domain. (A.L.B.)

Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

Science.gov (United States)

Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

2015-10-01

Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

Directory of Open Access Journals (Sweden)

Carlos A. Rubio

2014-01-01

Full Text Available The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014 exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days, by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease, collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.

Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

Science.gov (United States)

Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

2016-01-01

The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

[Knockdown of dopamine receptor D2 upregulates the expression of adiogenic genes in mouse primary mesencephalic neurons].

Science.gov (United States)

Ding, Jiaqi; Chen, Xiaoli; Lin, Jiaji; Zhu, Junling; Li, Zhuyi

2018-01-01

Objective To study the effects of dopamine receptor D2 (DRD2) on the adipogenesis genes in mouse primary mesencephalic neurons. Methods The lentiviral vectors which expressed specific shRNA targeting DRD2 were constructed to decrease DRD2 expression in mouse primary mesencephalic neurons. High throughput sequencing (HTS) analysis was used to investigate gene expression changes between the DRD2 knock-down group and the negative control group. Real-time quantitative PCR (qRT-PCR) and Western blot analysis were applied to verify the differently expressed genes. Fatty acids were measured by fatty acid detection kit. Results DRD2 expression was effectively down-regulated in mouse primary mesencephalic neurons by lentiviral vectors. HTS revealed adipogenesis genes were significantly up-regulated after DRD2 down-regulation, mainly including delta(14)-sterol reductase, acetyl-coenzyme A synthetase, insulin-induced gene 1 protein and especially stearoyl-coenzyme A desaturase 1 (SCD1, 4-fold upregulated). The qRT-PCR and Western blot analysis verified that SCD1 was upregulated 2.6 folds and 2 folds respectively by lentiviral DRD2-shRNA vectors. Moreover, the SCD1-related free fatty acids were significantly more increased than the negative control group. Conclusion DRD2 in primary mesencephalic neurons had a significant regulative effect on the adipogenesis genes. The up-regulation of SCD1 can accelerate the conversion of saturated fatty acids to monounsaturated fatty acids and prevent the damage of lipid toxicity to cells.

Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo.

Science.gov (United States)

Koci, Lenka; Chlebova, Katarina; Hyzdalova, Martina; Hofmanova, Jirina; Jira, Miroslav; Kysela, Petr; Kozubik, Alois; Kala, Zdenek; Krejci, Pavel

2012-04-01

Apoptosis inhibitor 5 (API-5) is a 55 kDa nuclear protein with potent anti-apoptotic signaling in tumor cells in vitro. In this study, we analyzed the expression of the API-5 protein in vivo in a broad spectrum of human carcinomas, including those of the colon, lung, liver, kidney, pancreas, stomach and esophagus using tumor tissues obtained during tumor resection. The results showed significant upregulation of API-5 expression in biopsies of lung (23%, n=13) and colorectal tumors (33%, n=27) in comparison with biopsies from the adjacent normal tissue. Colon cancer biopsies were used to study the cell populations with an upregulated level of expression of API-5 more closely. Using a magnetic bead-based selection for the epithelial cell marker EpCAM, we purified epithelial cells from the tumor and control tissues and analyzed these cells for API-5 expression by western immunoblotting. We observed that EpCAM-positive tumor cells expressed API-5 in all three colorectal cancer cases tested, in contrast to the control EpCAM-positive and EpCAM-negative cells isolated from the control or tumor tissues. These data suggest that the expression of the API-5 protein is upregulated in tumor epithelial cells and may serve as a prognostic marker in colorectal cancer.

Neural cell 3D microtissue formation is marked by cytokines' up-regulation.

Directory of Open Access Journals (Sweden)

Yinzhi Lai

Full Text Available Cells cultured in three dimensional (3D scaffolds as opposed to traditional two-dimensional (2D substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate. Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.

Sustaining the wild equals sustaining the world.

Science.gov (United States)

Nelson, G

1994-01-01

Sustainable development and carrying capacity are concepts that denote meeting society's needs without compromising the survival of future generations. The United States and other industrialized countries are pursuing a self-destructive course when fueling their economies by consuming their capital and degrading and depleting their resource base. Maximum exploitation of all resources has been the guiding ethic without paying respect to the environmental consequences. A sustainable society is still possible if strong political leadership and an ecologically literate society with an environmental ethic evolves. In the 1990s the world's population is calculated to increase to 6.3 billion people, the population of the United States already exceeds its carrying capacity and neither of these population increases are sustainable in the long run. In 1916 the US had 98 million people, and in 1994 it had about 260 million and it is still growing. The consequences are already obvious: the National Park System had just 358,000 visitors in 1916, 33 million in 1950, 172 million in 1970, and over 270 million in 1993. Often economists are an impediment to a sustainable economy because they fail to factor in the accumulated environmental deficit or annual cost of environmental deterioration when measuring annual economic output. Fortunately, in the US a conservation ethic is beginning to develop that will eventually become a strong social, political, and economic force. For instance, Wisconsin has mandated environmental education in every school from kindergarten through 12th grade. Such a program will provide the moral and political support to move the country to a sustainable economy. Even losing nations have recovered from World War II, but there is no recovery from destroyed ecosystems.

Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

DEFF Research Database (Denmark)

Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard

2014-01-01

BACKGROUND: Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB...... and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...

Sustainable Transition

DEFF Research Database (Denmark)

Hansen, Ole Erik; Søndergård, Bent

2014-01-01

of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

Sustainability Labeling

NARCIS (Netherlands)

Dam, van Y.K.

2017-01-01

Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

Life Cycle Sustainability Dashboard

DEFF Research Database (Denmark)

Traverso, Marzia; Finkbeiner, Matthias; Jørgensen, Andreas

2012-01-01

One method to assess the sustainability performance of products is life cycle sustainability assessment (LCSA), which assesses product performance considering the environmental,economic, and social dimensions of the life cycle. The results of LCSA can be used to compare different products...... of sustainability is the communicability of the results by means of a graphical representation (a cartogram), characterized by a suitable chromatic scale and ranking score. The integration of LCSA and the dashboard of sustainability into a so-called Life Cycle Sustainability Dashboard (LCSD) is described here...

Nanotechnology for sustainability: what does nanotechnology offer to address complex sustainability problems?

Energy Technology Data Exchange (ETDEWEB)

Wiek, Arnim, E-mail: arnim.wiek@asu.edu; Foley, Rider W. [Arizona State University, School of Sustainability (United States); Guston, David H. [Arizona State University, Center for Nanotechnology in Society, Consortium for Science, Policy and Outcomes (United States)

2012-09-15

Nanotechnology is widely associated with the promise of positively contributing to sustainability. However, this view often focuses on end-of-pipe applications, for instance, for water purification or energy efficiency, and relies on a narrow concept of sustainability. Approaching sustainability problems and solution options from a comprehensive and systemic perspective instead may yield quite different conclusions about the contribution of nanotechnology to sustainability. This study conceptualizes sustainability problems as complex constellations with several potential intervention points and amenable to different solution options. The study presents results from interdisciplinary workshops and literature reviews that appraise the contribution of the selected nanotechnologies to mitigate such problems. The study focuses exemplarily on the urban context to make the appraisals tangible and relevant. The solution potential of nanotechnology is explored not only for well-known urban sustainability problems such as water contamination and energy use but also for less obvious ones such as childhood obesity. Results indicate not only potentials but also limitations of nanotechnology's contribution to sustainability and can inform anticipatory governance of nanotechnology in general, and in the urban context in particular.

Nanotechnology for sustainability: what does nanotechnology offer to address complex sustainability problems?

International Nuclear Information System (INIS)

Wiek, Arnim; Foley, Rider W.; Guston, David H.

2012-01-01

Nanotechnology is widely associated with the promise of positively contributing to sustainability. However, this view often focuses on end-of-pipe applications, for instance, for water purification or energy efficiency, and relies on a narrow concept of sustainability. Approaching sustainability problems and solution options from a comprehensive and systemic perspective instead may yield quite different conclusions about the contribution of nanotechnology to sustainability. This study conceptualizes sustainability problems as complex constellations with several potential intervention points and amenable to different solution options. The study presents results from interdisciplinary workshops and literature reviews that appraise the contribution of the selected nanotechnologies to mitigate such problems. The study focuses exemplarily on the urban context to make the appraisals tangible and relevant. The solution potential of nanotechnology is explored not only for well-known urban sustainability problems such as water contamination and energy use but also for less obvious ones such as childhood obesity. Results indicate not only potentials but also limitations of nanotechnology’s contribution to sustainability and can inform anticipatory governance of nanotechnology in general, and in the urban context in particular.

Sustainability or Bust: Malaysian Home Buyers’ Stated Preferences for Sus-Tainable Housing

Directory of Open Access Journals (Sweden)

Syahid A.

2016-01-01

Full Text Available The lack of data on sustainable home buying behaviour in developing countries such as Malaysia is due to the absence of sustainable housing itself. However, it is still possible to solicit home buyers for their stated preferences and quantify its effects on housing demand. In this study, a sample of 300 responses to a Discrete Choice Experiment (DCE on sustainable housing features was analysed using the “support.CEs” program. This study found that the addition of sustainable features; renewable energy generation, enhanced soundproofing and ventilation, energy saving features, and higher green area ratios significantly increase home buyer’s willingness to pay (WTP for sustainable housing.

The Psychology of Sustainability and Sustainable Development for Well-Being in Organizations.

Science.gov (United States)

Di Fabio, Annamaria

2017-01-01

This article discusses the contribution of the psychology of sustainability and sustainable development to well-being in organizations from a primary prevention perspective. It deals with sustainability not only in terms of the ecological, economic, and social environment but also in terms of improving the quality of life of every human being. The psychology of sustainability and sustainable development is seen as a primary prevention perspective that can foster well-being in organizations at all the different levels going from the worker, to the group, to the organization, and also to inter-organizational processes. The possibilities for further research and interventions are also discussed.

β2-Adrenergic Receptor-Mediated HIF-1α Upregulation Mediates Blood Brain Barrier Damage in Acute Cerebral Ischemia

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Yanyun Sun

2017-08-01

Full Text Available Disruption of the blood brain barrier (BBB within the thrombolytic time window is an antecedent event to intracerebral hemorrhage in ischemic stroke. Our recent studies showed that 2-h cerebral ischemia induced BBB damage in non-infarcted area and secreted matrix metalloproteinase-2 (MMP-2 accounted for this disruption. However, the factors that affect MMP-2 secretion and regulate BBB damage remains unknown. Since hypoxia-inducible factor-1 alpha (HIF-1α was discovered as a mater regulator in hypoxia, we sought to investigate the roles of HIF-1α in BBB damage as well as the factors regulating HIF-1α expression in the ischemic brain. in vivo rat middle cerebral artery occlusion (MCAO and in vitro oxygen glucose deprivation (OGD models were used to mimic ischemia. Pretreatment with HIF-1α inhibitor YC-1 significantly inhibited 2-h MCAO-induced BBB damage, which was accompanied by suppressed occludin degradation and vascular endothelial growth factor (VEGF mRNA upregulation. Interestingly, β2-adrenergic receptor (β2-AR antagonist ICI 118551 attenuated ischemia-induced BBB damage by regulating HIF-1α expression. Double immunostaining showed that HIF-1α was upregulated in ischemic neurons but not in astrocytes andendothelial cells. Of note, HIF-1α inhibition with inhibitor YC-1 or siRNA significantly prevented OGD-induced VEGF upregulation as well as the secretion of VEGF and MMP-2 in neurons. More importantly, blocking β2-AR with ICI 118551 suppressedHIF-1α upregulation in ischemic neurons and attenuated occludin degradation induced by the conditioned media of OGD-treatedneurons. Taken together, blockade of β2-AR-mediated HIF-1α upregulation mediates BBB damage during acute cerebral ischemia. These findings provide new mechanistic understanding of early BBB damage in ischemic stroke and may help reduce thrombolysis-related hemorrhagic complications.

Dual-Specificity Phosphatase 4 Overexpression in Cells Prevents Hypoxia/Reoxygenation-Induced Apoptosis via the Upregulation of eNOS

Science.gov (United States)

Dougherty, Julie A.; Kilbane Myers, Joanna; Khan, Mahmood; Angelos, Mark G.; Chen, Chun-An

2017-01-01

Mitogen-activated protein kinases (MAPKs) signaling cascades regulate several cellular functions, including differentiation, proliferation, survival, and apoptosis. The duration and magnitude of phosphorylation of these MAPKs are decisive determinants of their physiological functions. Dual-specificity phosphatases exert kinetic control over these signaling cascades. Previously, we demonstrated that DUSP4−/− hearts sustain a larger infarct and have poor functional recovery, when isolated hearts were subjected to ischemia/reperfusion. Uncontrolled p38 activation and upregulation of Nox4 expression are the main effectors for this functional alteration. Here, dual-specificity phosphatase 4 (DUSP4) overexpression in endothelial cells was used to investigate the role of DUSP4 on the modulation of reactive oxygen species (ROS) generation and vascular function, when cells were subjected to hypoxia/reoxygenation (H/R) insult. Immunostaining with cleaved caspase-3 revealed that DUSP4 overexpression prevents caspase-3 activation and apoptosis after H/R. The beneficial effects occur via modulating p38 activity, increased NO bioavailability, and reduced oxidative stress. More importantly, DUSP4 overexpression upregulates eNOS protein expression (1.62 ± 0.33 versus 0.65 ± 0.16) during H/R-induced stress. NO is a critical small molecule involved in regulating vascular tone, vascular growth, platelet aggregation, and modulation of inflammation. The level of NO generation determined using DAF-2 fluorescence demonstrated that DUSP4 overexpression augments NO production and thus improves vascular function. The level of superoxide generated from cells after being subjected to H/R was determined using dihydroethidium-HPLC method. The results suggested that DUSP4 overexpression in cells decreases H/R-induced superoxide generation (1.56 ± 0.14 versus 1.19 ± 0.05) and thus reduces oxidant stress. This also correlates with the reduction in the total protein S

Sustainable transformation

DEFF Research Database (Denmark)

Andersen, Nicolai Bo

This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuil...

Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

Directory of Open Access Journals (Sweden)

Yoon TH

2012-03-01

Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

Towards sustainability assessment follow-up

Energy Technology Data Exchange (ETDEWEB)

Morrison-Saunders, Angus, E-mail: a.morrison-saunders@murdoch.edu.au [Murdoch University (Australia); North-West University (South Africa); Pope, Jenny, E-mail: jenny@integral-sustainability.net [North-West University (South Africa); Integral Sustainability (Australia); Curtin University (Australia); Bond, Alan, E-mail: alan.bond@uea.ac.uk [North-West University (South Africa); University of East Anglia (United Kingdom); Retief, Francois, E-mail: francois.retief@nwu.ac.za [North-West University (South Africa)

2014-02-15

This paper conceptualises what sustainability assessment follow-up might entail for three models of sustainability assessment: EIA-driven integrated assessment, objectives-led integrated assessment and the contribution to sustainability model. The first two are characterised by proponent monitoring and evaluation of individual impacts and indicators while the latter takes a holistic view based around focused sustainability criteria relevant to the context. The implications of three sustainability challenges on follow-up are also examined: contested time horizons and value changes, trade-offs, and interdisciplinarity. We conclude that in order to meet these challenges some form of adaptive follow-up is necessary and that the contribution to sustainability approach is the best approach. -- Highlights: • We explore sustainability follow-up for three different sustainability models. • Long-time frames require adaptive follow-up and are a key follow-up challenge. • Other key challenges include interdisciplinarity, and trade-offs. • Sustainability follow-up should be a direction of travel and not an outcome. • Only the follow-up for contribution to sustainability model addresses sustainability challenges sufficiently.

Towards sustainability assessment follow-up

International Nuclear Information System (INIS)

Morrison-Saunders, Angus; Pope, Jenny; Bond, Alan; Retief, Francois

2014-01-01

This paper conceptualises what sustainability assessment follow-up might entail for three models of sustainability assessment: EIA-driven integrated assessment, objectives-led integrated assessment and the contribution to sustainability model. The first two are characterised by proponent monitoring and evaluation of individual impacts and indicators while the latter takes a holistic view based around focused sustainability criteria relevant to the context. The implications of three sustainability challenges on follow-up are also examined: contested time horizons and value changes, trade-offs, and interdisciplinarity. We conclude that in order to meet these challenges some form of adaptive follow-up is necessary and that the contribution to sustainability approach is the best approach. -- Highlights: • We explore sustainability follow-up for three different sustainability models. • Long-time frames require adaptive follow-up and are a key follow-up challenge. • Other key challenges include interdisciplinarity, and trade-offs. • Sustainability follow-up should be a direction of travel and not an outcome. • Only the follow-up for contribution to sustainability model addresses sustainability challenges sufficiently

Healthcare Building Sustainability Assessment tool - Sustainable Effective Design criteria in the Portuguese context

International Nuclear Information System (INIS)

Castro, Maria de Fátima; Mateus, Ricardo; Bragança, Luís

2017-01-01

Tools and methods to improve current practices and quality in the healthcare building sector are necessary to support decision-making at different building life cycle phases. Furthermore, Healthcare Building Sustainability Assessment (HBSA) Methods are based on criteria organised into different levels, such as categories and indicators. These criteria highlight aspects of significant importance when designing and operating a sustainable healthcare building. To bring more objectivity to the sustainability assessments, the standardisation bodies (CEN and ISO) proposed core indicators that should be used in the evaluation of the environmental, societal and economic performances of buildings. Nevertheless, relying on state of the art analysis, it is possible to conclude that there are aspects of major importance for the operation of healthcare buildings that are not considered in the HBSA methods. Thus, the aim of this paper is to discuss the context of sustainability assessment methods in the field of healthcare buildings and to present a proposal for the incorporation of Sustainable-Effective Design (SED) criteria in a new HBSA method. The used research method is innovative since in the development of the list of sustainability criteria it considers the opinion of main healthcare buildings' stakeholders, the existing healthcare assessment methods and the ISO and CEN standardisation works in the field of the methods to assess the sustainability of construction works. As a result, the proposed method is composed of fifty-two sustainability indicators that cover the different dimensions of the sustainability concept to support decision making during the design of a new or retrofitted healthcare building in urban areas. - Highlights: •A new system to assess the sustainability of healthcare buildings is presented. •We propose a method to develop the list of sustainability indicators for hospitals. •We propose a new concept – Sustainable-Effective Design (SED

Review of sustainability indices and indicators: Towards a new City Sustainability Index (CSI)

Energy Technology Data Exchange (ETDEWEB)

Mori, Koichiro, E-mail: kmori@iis.u-tokyo.ac.jp [Institute of Industrial Science, University of Tokyo (Japan); Christodoulou, Aris, E-mail: aris.christodoulou@ucl.ac.uk [Centre for Transport Studies, University College London (United Kingdom)

2012-01-15

The purpose of this paper is to discuss conceptual requirements for a City Sustainability Index (CSI) and to review existing major sustainability indices/indicators in terms of the requirements. The following indices are reviewed: Ecological Footprint (EF), Environmental Sustainability Index (ESI), Dashboard of Sustainability (DS), Welfare Index, Genuine Progress Indicator (GPI), Index of Sustainable Economic Welfare, City Development Index, emergy/exergy, Human Development Index (HDI), Environmental Vulnerability Index (EVI), Environmental Policy Index (EPI), Living Planet Index (LPI), Environmentally-adjusted Domestic Product (EDP), Genuine Saving (GS), and some applications of composite indices or/and multivariate indicators to local or regional context as case studies. The key conceptual requirements for an adequate CSI are: (i) to consider environmental, economic and social aspects (the triple bottom line of sustainability) from the viewpoint of strong sustainability; (ii) to capture external impacts (leakage effects) of city on other areas beyond the city boundaries particularly in terms of environmental aspects; (iii) to create indices/indicators originally for the purpose of assessing city sustainability; and (iv) to be able to assess world cities in both developed and developing countries using common axes of evaluation. Based on the review, we conclude that it is necessary to create a new CSI that enables us to assess and compare cities' sustainability performance in order to understand the global impact of cities on the environment and human life as compared with their economic contribution. In the future, the CSI will be able to provide local authorities with guidance toward sustainable paths. - Highlights: Black-Right-Pointing-Pointer We derive the four key requirements for a new City Sustainability Index (CSI) system. Black-Right-Pointing-Pointer First, the triple bottom line must be considered in terms of strong sustainability. Black

Review of sustainability indices and indicators: Towards a new City Sustainability Index (CSI)

International Nuclear Information System (INIS)

Mori, Koichiro; Christodoulou, Aris

2012-01-01

The purpose of this paper is to discuss conceptual requirements for a City Sustainability Index (CSI) and to review existing major sustainability indices/indicators in terms of the requirements. The following indices are reviewed: Ecological Footprint (EF), Environmental Sustainability Index (ESI), Dashboard of Sustainability (DS), Welfare Index, Genuine Progress Indicator (GPI), Index of Sustainable Economic Welfare, City Development Index, emergy/exergy, Human Development Index (HDI), Environmental Vulnerability Index (EVI), Environmental Policy Index (EPI), Living Planet Index (LPI), Environmentally-adjusted Domestic Product (EDP), Genuine Saving (GS), and some applications of composite indices or/and multivariate indicators to local or regional context as case studies. The key conceptual requirements for an adequate CSI are: (i) to consider environmental, economic and social aspects (the triple bottom line of sustainability) from the viewpoint of strong sustainability; (ii) to capture external impacts (leakage effects) of city on other areas beyond the city boundaries particularly in terms of environmental aspects; (iii) to create indices/indicators originally for the purpose of assessing city sustainability; and (iv) to be able to assess world cities in both developed and developing countries using common axes of evaluation. Based on the review, we conclude that it is necessary to create a new CSI that enables us to assess and compare cities' sustainability performance in order to understand the global impact of cities on the environment and human life as compared with their economic contribution. In the future, the CSI will be able to provide local authorities with guidance toward sustainable paths. - Highlights: ► We derive the four key requirements for a new City Sustainability Index (CSI) system. ► First, the triple bottom line must be considered in terms of strong sustainability. ► Second, environmental leakage effects beyond city boundaries should

Is Mass Customization Sustainable?

DEFF Research Database (Denmark)

Petersen, Thomas Ditlev; Jørgensen, Kaj Asbjørn; Nielsen, Kjeld

2011-01-01

Mass customizers are like other companies currently experiencing an increasing customer demand for environmentally sustainable products as well as an increasingly strict legislation regarding environmental sustainability. This paper addresses the issue whether the concepts mass customization...... and sustainability are fundamentally compatible by asking the question: can a mass customized product be sustainable? Several factors could indicate that mass customized products are less sustainable than standardized products; however other factors suggest the opposite. This paper explores these factors during...... three life cycle phases for a product: Production, Use and End of Life. It is concluded that there is not an unambiguous causal relationship between mass customization and sustainability; however several factors unique to mass customized products are essential to consider during product and process...

Sustainable built environments

CERN Document Server

Haase, Dagmar

2013-01-01

Sustainable design is a collective process whereby the built environment achieves unprecedented levels of ecological balance through new and retrofit construction, with the goal of long-term viability and humanization of architecture. Focusing on the environmental context, sustainable design merges the natural, minimum resource conditioning solutions of the past (daylight, solar heat, and natural ventilation) with the innovative technologies of the present.  The desired result is an integrated “intelligent” system that supports individual control with expert negotiation for resource consciousness. International experts in the field address the fundamental questions of sustainable design and landscape management: How should the sustainability of landscapes and buildings be evaluated? Which targets have to be set and which thresholds should not be exceeded? What forms of planning and governance structures exist and to what extent do they further the goals of sustainability?  Gathering 30 peer-reviewed ent...

Sustainability index for Taipei

International Nuclear Information System (INIS)

Lee, Y.-J.; Huang Chingming

2007-01-01

Sustainability indicators are an effective means of determining whether a city is moving towards sustainable development (SD). After considering the characteristics of Taipei, Taiwan, discussions with experts, scholars and government departments and an exhaustive literature review, this study selected 51 sustainability indicators corresponding to the socio-economic characteristic of Taipei City. Such indicators should be regarded as a basis for assessing SD in Taipei City. The 51 indicators are classified into economic, social, environmental and institutional dimensions. Furthermore, statistical data is adopted to identify the trend of SD from 1994 to 2004. Moreover, the sustainability index is calculated for the four dimensions and for Taipei as a whole. Analysis results demonstrate that social and environmental indicators are moving towards SD, while economic and institutional dimensions are performing relatively poorly. However, since 2002, the economic sustainability index has gradually moved towards SD. Overall, the Taipei sustainability index indicates a gradual trend towards sustainable development during the past 11 years

The Sustainability Cycle and Loop: models for a more unified understanding of sustainability.

Science.gov (United States)

Hay, Laura; Duffy, Alex; Whitfield, R I

2014-01-15

In spite of the considerable research on sustainability, reports suggest that we are barely any closer to a more sustainable society. As such, there is an urgent need to improve the effectiveness of human efforts towards sustainability. A clearer and more unified understanding of sustainability among different people and sectors could help to facilitate this. This paper presents the results of an inductive literature investigation, aiming to develop models to explain the nature of sustainability in the Earth system, and how humans can effectively strive for it. The major contributions are two general and complementary models, that may be applied in any context to provide a common basis for understanding sustainability: the Sustainability Cycle (S-Cycle), and the Sustainability Loop (S-Loop). Literature spanning multiple sectors is examined from the perspective of three concepts, emerging as significant in relation to our aim. Systems are shown to provide the context for human action towards sustainability, and the nature of the Earth system and its sub-systems is explored. Activities are outlined as a fundamental target that humans need to sustain, since they produce the entities both needed and desired by society. The basic behaviour of activities operating in the Earth system is outlined. Finally, knowledge is positioned as the driver of human action towards sustainability, and the key components of knowledge involved are examined. The S-Cycle and S-Loop models are developed via a process of induction from the reviewed literature. The S-Cycle describes the operation of activities in a system from the perspective of sustainability. The sustainability of activities in a system depends upon the availability of resources, and the availability of resources depends upon the rate that activities consume and produce them. Humans may intervene in these dynamics via an iterative process of interpretation and action, described in the S-Loop model. The models are briefly

Moxibustion upregulates hippocampal progranulin expression

Directory of Open Access Journals (Sweden)

Tao Yi

2016-01-01

Full Text Available In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4 and Zusanli (ST36, bilateral were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

Sustainability Infused Curriculum

Science.gov (United States)

Ibarra, D. L.

2015-12-01

The Independent Schools Foundation Academy (ISF) in Hong Kong established a sustainability policy in 2015, which explicitly states, "an experimentally integrated, environmentally and ethically sustainable system of science education and conservation practices based on the 2012 Jeju Declaration of the World Conservation Congress will be implemented through the school". ISF Academy is a private Chinese bilingual school in Hong Kong serving over 1500 students K-12, following the framework and curriculum of the International Baccalaureate Organization (IBO). The strategy behind the implementation of this policy includes: development of a scientific sustainable curriculum that is age appropriate; establish a culture of sustainability within the ISF community and beyond to the wider HK community; install sustainable infrastructure that allows students to learn; and learn first hand sustainable living practices. It is well understood that solutions to the environmental challenges facing Hong Kong and our planet will require multiple disciplines. The current sustainability programs at ISF include: a) a whole school aerobic food waste composting system and organic farming, b) energy consumption monitoring of existing buildings, c) upcoming installation of an air pollution monitoring equipment that will correlate with the AQHI data collected by the Hong Kong government, d) a Renewable Energy Education Center (REEC) that will teach students about RE and also produce solar energy for classroom consumption, and e) student lead environmental group that manages the paper and used cooking oil recycling on campus. The Shuyuan Science and Sustainability faculty work closely with classroom teachers to ensure that the above mentioned projects are incorporated into the curriculum throughout the school. Interdisciplinary units (IDU) of study are being developed that encourage faculty and students to work across subject areas. Projects include Personal Projects, Extended Essays

Pluralism in Search of Sustainability: Ethics, Knowledge and Methdology in Sustainability Science

Directory of Open Access Journals (Sweden)

Ellinor Isgren

2017-02-01

Full Text Available Sustainability Science is an emerging, transdisciplinary academic field that aims to help build a sustainable global society by drawing on and integrating research from the humanities and the social, natural, medical and engineering sciences. Academic knowledge is combined with that from relevant actors from outside academia, such as policy-makers, businesses, social organizations and citizens. The field is focused on examining the interactions between human, environmental, and engineered systems to understand and contribute to solutions for complex challenges that threaten the future of humanity and the integrity of the life support systems of the planet, such as climate change, biodiversity loss, pollution, and land and water degradation. Since its inception in around the year 2000, and as expressed by a range of proponents in the field, sustainability science has become an established international platform for interdisciplinary research on complex social problems [1]. This has been done by exploring ways to promote ‘greater integration and cooperation in fulfilling the sustainability science mandate’ [2]. Sustainability science has thereby become an extremely diverse academic field, yet one with an explicit normative mission. After nearly two decades of sustainability research, it is important to reflect on a major question: what critical knowledge can we gain from sustainability science research on persistent socio-ecological problems and new sustainability challenges?

A pathway to a more sustainable water sector: sustainability-based asset management.

Science.gov (United States)

Marlow, D R; Beale, D J; Burn, S

2010-01-01

The water sectors of many countries are faced with the need to address simultaneously two overarching challenges; the need to undertake effective asset management coupled with the broader need to evolve business processes so as to embrace sustainability principles. Research has thus been undertaken into the role sustainability principles play in asset management. As part of this research, a series of 25 in-depth interviews were undertaken with water sector professionals from around Australia. Drawing on the results of these interviews, this paper outlines the conceptual relationship between asset management and sustainability along with a synthesis of the relevant opinions voiced in the interviews. The interviews indicated that the participating water authorities have made a strong commitment to sustainability, but there is a need to facilitate change processes to embed sustainability principles into business as usual practices. Interviewees also noted that asset management and sustainability are interlinked from a number of perspectives, especially in the way decision making is undertaken with respect to assets and service provision. The interviews also provided insights into the research needed to develop a holistic sustainability-based asset management framework.

Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage

DEFF Research Database (Denmark)

Povlsen, Gro Klitgaard; Johansson, Sara Ellinor; Larsen, Carl Christian

2013-01-01

shown to be mediated by intracellular signalling via the mitogen activated protein kinase kinase (MEK1/2)--extracellular regulated kinase 1/2 (ERK1/2) pathway. However, it is not known what event(s) that trigger MEK-ERK1/2 activation and vasoconstrictor receptor upregulation after SAH.We hypothesise...

Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis

Directory of Open Access Journals (Sweden)

Karin Zins

2014-01-01

Full Text Available The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death.

Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

Science.gov (United States)

McPartland, John M; Guy, Geoffrey W; Di Marzo, Vincenzo

2014-01-01

The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

Interpreting Sustainability for Urban Forests

Directory of Open Access Journals (Sweden)

Camilo Ordóñez

2010-06-01

Full Text Available Incisive interpretations of urban-forest sustainability are important in furthering our understanding of how to sustain the myriad values associated with urban forests. Our analysis of earlier interpretations reveals conceptual gaps. These interpretations are attached to restrictive definitions of a sustainable urban forest and limited to a rather mechanical view of maintaining the biophysical structure of trees. The probing of three conceptual domains (urban forest concepts, sustainable development, and sustainable forest management leads to a broader interpretation of urban-forest sustainability as the process of sustaining urban forest values through time and across space. We propose that values—and not services, benefits, functions or goods—is a superior concept to refer to what is to be sustained in and by an urban forest.

Reciprocal upregulation of Notch signaling molecules in hematopoietic progenitor and mesenchymal stromal cells

Directory of Open Access Journals (Sweden)

Kikuchi Y

2011-01-01

Full Text Available Although mesenchymal stem cells (MSCs play pivotal supportive roles in hematopoiesis, how they interact with hematopoietic stem cells (HSCs is not well understood. We investigated the interaction between HSCs and surrogate MSCs (C3H10T1/2 stromal cells, focusing on the molecular events induced by cell contact of these bipartite populations. C3H10T1/2 is a mesenchymal stromal cell line that can be induced to differentiate into preadipocytes (A54 and myoblasts (M1601. The stromal cell derivatives were cocultured with murine HSCs (Lineage-Sca1+, and gene expression profiles in stromal cells and HSCs were compared before and after the coculture. HSCs gave rise to cobblestone areas only on A54 cells, with ninefold more progenitors than on M1601 or undifferentiated C3H10T1/2 cells. Microarray-based screening and a quantitative reverse transcriptase directed-polymerase chain reaction showed that the levels of Notch ligands (Jagged1 and Delta-like 3 were increased in A54 cells upon interaction with HSCs. On the other hand, the expression of Notch1 and Hes1 was upregulated in the HSCs cocultured with A54 cells. A transwell assay revealed that the reciprocal upregulation was dependent on cell-to-cell contact. The result suggested that in the hematopoietic niche, HSCs help MSCs to produce Notch ligands, and in turn, MSCs help HSCs to express Notch receptor. Such a reciprocal upregulation would reinforce the downstream signaling to determine the fate of hematopoietic cell lineage. Clarification of the initiating events on cell contact should lead to the identification of specific molecular targets to facilitate HSC engraftment in transplantation therapy.

Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss.

Science.gov (United States)

Baldo, Brian A; Hanlon, Erin C; Obermeyer, William; Bremer, Quentin; Paletz, Elliott; Benca, Ruth M

2013-12-01

Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Energy Technology Data Exchange (ETDEWEB)

Luo, Shuang, E-mail: luoshuangsch@163.com [Department of Obstetrics and Gynecology, Suining Central Hospital, Suining (China); Wang, Jidong [Department of Gynecology and Obsterics, Jinan Central Hospital, Jinan (China); Ma, Ying [Department of Otorhinolaryngolgy, Suining Central Hospital, Suining (China); Yao, Zhenwei [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Pan, Hongjuan [Department of Gynecology and Obsterics, Zhongshan Hospital, Wuhan (China)

2015-06-26

miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence of miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.

Sustainability issues in civil engineering

CERN Document Server

Saride, Sireesh; Basha, B

2017-01-01

This compilation on sustainability issues in civil engineering comprises contributions from international experts who have been working in the area of sustainability in civil engineering. Many of the contributions have been presented as keynote lectures at the International Conference on Sustainable Civil Infrastructure (ICSCI) held in Hyderabad, India. The book has been divided into core themes of Sustainable Transportation Systems, Sustainable Geosystems, Sustainable Environmental and Water Resources and Sustainable Structural Systems. Use of sustainability principles in engineering has become an important component of the process of design and in this context, design and analysis approaches in civil engineering are being reexamined to incorporate the principles of sustainable designs and construction in practice. Developing economies are on the threshold of rapid infrastructure growth and there is a need to compile the developments in various branches of civil engineering and highlight the issues. It is th...

Rapid upregulation of heart antioxidant enzymes during arousal from estivation in the Giant African snail (Achatina fulica).

Science.gov (United States)

Salway, Kurtis D; Tattersall, Glenn J; Stuart, Jeffrey A

2010-11-01

Estivation is an adaptive response to environments characterized by elevated temperatures and desiccative stress, as may occur during summer dry seasons. Similar to diapause and hibernation, it is characterized by low levels of activity, a drastically suppressed metabolic rate and enhanced stress resistance. We tested the hypothesis that Achatina fulica, a pulmonate land snail, enhances stress resistance during estivation and/or arousal by upregulating intracellular antioxidant defenses in the heart, kidney, hepatopancreas and foot tissues. No statistically significant changes in mitochondrial or cytosolic superoxide dismutase levels or activities, or glutathione peroxidase, glutathione reductase or catalase activities were associated with estivation in any tissue, however. In contrast, during arousal from estivation, activities of several antioxidant enzymes increased in heart, hepatopancreas and foot. In heart, a rapid increase in MnSOD protein levels was observed that peaked at 2h post arousal, but no such change was observed in CuZnSOD protein levels. Glutathione peroxidase activity was upregulated at 1h post arousal and remained elevated until 8h post arousal in heart tissue. Glutathione peroxidase was also upregulated at 24h post arousal in foot tissue. Glutathione reductase activity was upregulated at 4h post arousal in heart and foot tissues whereas catalase activity showed no changes. Markers of lipid peroxidation and protein damage revealed no significant increases during estivation or arousal. Therefore, antioxidant enzymes may play a role in oxidative stress defense specifically during arousal from estivation in A. fulica. Copyright 2010 Elsevier Inc. All rights reserved.

Packaging for Sustainability

CERN Document Server

Lewis, Helen; Fitzpatrick, Leanne

2012-01-01

The packaging industry is under pressure from regulators, customers and other stakeholders to improve packaging’s sustainability by reducing its environmental and societal impacts. This is a considerable challenge because of the complex interactions between products and their packaging, and the many roles that packaging plays in the supply chain. Packaging for Sustainability is a concise and readable handbook for practitioners who are trying to implement sustainability strategies for packaging. Industry case studies are used throughout the book to illustrate possible applications and scenarios. Packaging for Sustainability draws on the expertise of researchers and industry practitioners to provide information on business benefits, environmental issues and priorities, environmental evaluation tools, design for environment, marketing strategies, and challenges for the future.

Sustainability in Transport Planning

DEFF Research Database (Denmark)

Gudmundsson, Henrik; Greve, Carsten

Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

From Corporate Social Responsibility to Corporate Sustainability: Features of Financing Sustainable Development

Directory of Open Access Journals (Sweden)

Vasylchuk Irуna P.

2018-03-01

Full Text Available The theoretical basis of the concepts of corporate social responsibility and sustainable development are studied. It is revealed that scientists mainly distinguish two main stages in the evolution of the concept of corporate social responsibility. There argued the expediency of singling out the third stage of the development of the concept (version CSR 2.0, which is characterized by the integration of the theoretical and practical foundations of the concepts of CSR and sustainable development as well as by their implementation into activities of corporations. The presence of the necessary prerequisites for singling out the new stage in the evolution of these concepts (version CSR 3.0, which is based on the provisions of the collaborative theory and provides for the cooperation of social enterprises and sustainable corporations in achieving the goals of sustainable development, is revealed, its expediency is justified. The determinant of the stage is the use of opportunities for sustainable development, the dominant is the social orientation, and its content is characterized by the slogan “doing common good to do common well”. Using generalization, there identified the features of the established models of sustainable development of corporations by key aspects (goals, principles, methods. On this basis, the features of approaches to financing sustainable development at the macro and micro levels are determined, and the principles for financing the activities of corporations in the new conditions are defined. It is concluded that achieving sustainability requires an effective system of financing corporate measures aimed at sustainable development, for the creation of which in Ukraine it is necessary to use the experience of “best practices” at the national, local and corporate levels.

Using Sustainability Engineering to Gain Universal Sustainability Efficiency

Directory of Open Access Journals (Sweden)

Aleksandras Vytautas Rutkauskas

2012-05-01

Full Text Available The present article is an attempt to perceive the universal sustainability observable in an individual country or region, where the religious, political, social-demographic, economic, environmental, creative, technological and investment subsystems are revealed not only through the vitality of spiritual and material existence media, but rather through the signs of the development of these subsystems as self-assembled units through the erosion of their interaction. The problem of optimal allocation of investment resources among the separate sustainability’s subsystems was addressed by means of expert methods and techniques of portfolio methodology which will enable the achievement of the enshrined universal sustainability standards. A country-specific index composition of sustainability subsystems’ indices was chosen as the universal sustainability index for the specific country. The index in its dynamics is perceived as a random process. While projecting its state and evaluating its power, i.e., the impact of the subsystem efficiency in a particular moment, this power is measured by the level of the index and the reliability or guarantee of an appropriate level. To solve the problem of investment resources allocation, the idea of Markowitz Random Field was invoked in order to reach the maximum power of sustainability index while applying the technical solution—the so-called “GoldSim” system. Engineering is a methodology that aspires to reveal the core attributes of complex systems and instruments in order to manage the possibility to influence these properties for the systems. Experimental expert evaluation and case study is performed on Lithuanian data.

Education for sustainable development. Just do it : guide to designing education for sustainable development

NARCIS (Netherlands)

Frijters, S.

Sustainable development has become a crucial part of our modern society and our education. Sustainability is a complex concept. After all, what is considered sustainable to us now may not necessarily be so in the future. We need to continually review our judgments with regards to sustainability.

ICT innovations for sustainability

CERN Document Server

Aebischer, Bernard

2015-01-01

ICT Innovations for Sustainability is an investigation of how information and communication technology can contribute to sustainable development. It presents clear definitions of sustainability, suggesting conceptual frameworks for the positive and negative effects of ICT on sustainable development. It reviews methods of assessing the direct and indirect impact of ICT systems on energy and materials demand, and examines the results of such assessments. In addition, it investigates ICT-based approaches to supporting sustainable patterns of production and consumption, analyzing them at various levels of abstraction – from end-user devices, Internet infrastructure, user behavior, and social practices to macro-economic indicators.   Combining approaches from Computer Science, Information Systems, Human-Computer Interaction, Economics, and Environmental Sciences, the book presents a new, holistic perspective on ICT for Sustainability (ICT4S). It is an indispensable resource for anyone working in the area of ICT...

Insulin-like growth factor 2 (IGF2) modulates murine hematopoietic stem cell maintenance through upregulation of p57

Science.gov (United States)

Thomas, Dolly D.; Sommer, Andreia Gianotti; Balazs, Alejandro B.; Beerman, Isabel; Murphy, George J.; Rossi, Derrick; Mostoslavsky, Gustavo

2017-01-01

Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found Insulin-like growth factor 2 (IGF2) to be predominantly expressed within long-term HSC. This study examines IGF2 expression patterns and the effects of the gene in HSC. Through the overexpression and knockdown of IGF2 within purified HSC, we demonstrate that IGF2 expression increases HSC-derived multilineage colonies in vitro and enhances hematopoietic contribution in vivo upon competitive bone marrow transplantation. The effects of IGF2 are mediated by direct upregulation of the CDKi p57, exclusively within long-term HSC, via activation of the PI3K-Akt pathway. Increased expression of p57 resulted in a concomitant increase of HSC in the G0/G1 stage of the cell cycle. Analysis of genomic DNA methylation revealed that HSC exhibited a hypomethylated state within the promoter region of the CDKN1C (p57) gene, providing a potential mechanism for the exclusive effects of IGF2 within HSC. Our studies demonstrate a novel role for IGF2 in regulating HSC cell cycle and illustrate potential novel therapeutic targets for hematological diseases. PMID:26872540

Sustainability of abrasive processes

DEFF Research Database (Denmark)

Aurich, J.C.; Linke, B.; Hauschild, Michael Zwicky

2013-01-01

, the content of technical presentations in STC G, and the results of a comprehensive literature study. The approach to sustainability includes environmental, social, and economic sustainability in accordance with the definition proposed in the Brundtland Report of the United Nations [156]. The main focus......This paper presents an overview of research on sustainability of abrasive processes. It incorporates results from a round robin study on ‘‘energy-efficiency of abrasive processes’’ which has been carried out within the scientific technical committee ‘‘abrasive processes’’ (STC G) of CIRP...... is on environmental and social sustainability. Economic sustainability will be considered as manufacturing productivity. © 2013 CIRP....

PATHWAYS TO SUSTAINABLE BANKING MANAGEMENT

Directory of Open Access Journals (Sweden)

Dragan (Santamarian Oana Raluca

2012-12-01

Full Text Available This paper describes one of the major challenges of the future: the sustainable development of the society. Sustainability is now increasingly recognized as central to the growth of emerging market economies. For the banking sector, this represents both a demand for greater social and environmental responsibility as well as a new landscape of business opportunity. Several years ago, the main part of the banks did not consider the social and environmental problems relevant for their operations. Recently, the banks began to realize the major impact of the sustainable development over the way of ulterior development of the society and, implicitly over the way of creating of the banking value in the future. In this context, the development of a banking management system, based on sustainable principles represents one of the provocations of these days.Starting from literature in the sustainable banking management field in this paper are presented several relevant issues related to risk management in the context of sustainable banking financing: the need to implement the sustainable management principles in financial and banking industry; the role of banks in sustainable development of society; social and environmental risk management policies, events that have shaped the role of the banking sector in sustainable development; international standards regarding sustainable banking management such us: Equator Principles for sustainable investment projects’ financing or GRI principles for sustainable reporting. Furthermore, we developed a practical case study related to the implementation of sustainable banking management at Bank of America.

Chitosan oligosaccharide and salicylic acid up-regulate gene expression differently in relation to the biosynthesis of artemisinin in Artemisia annua L

DEFF Research Database (Denmark)

Yin, Heng; Kjær, Anders; Fretté, Xavier

2012-01-01

oligosaccharide (COS) and salicylic acid (SA) on both artemisinin production and gene expression related to the biosynthetic pathway of artemisinin. COS up-regulated the transcriptional levels of the genes ADS and TTG1 2.5 fold and 1.8 fold after 48 h individually, whereas SA only up-regulated ADS 2.0 fold after...

The Fe/S Cluster Assembly Protein Isd11 Is Essential for tRNA Thiolation in Trypanosoma brucei

Czech Academy of Sciences Publication Activity Database

Paris, Zdeněk; Changmai, Piya; RUBIO, M. A. T.; Zíková, Alena; Stuart, K. D.; Alfonzo, J. D.; Lukeš, Julius

2010-01-01

Roč. 285, č. 29 (2010), s. 22394-22402 ISSN 0021-9258 R&D Projects: GA ČR GA204/09/1667 Institutional research plan: CEZ:AV0Z60220518 Keywords : IRON-SULFUR PROTEINS * SACCHAROMYCES-CEREVISIAE * CYSTEINE DESULFURASE * THIO- MODIFICATION * FRATAXIN Subject RIV: EB - Genetic s ; Molecular Biology Impact factor: 5.328, year: 2010

Sustainability : Politics and governance

NARCIS (Netherlands)

Heinrichs, Harald; Biermann, Frank

2016-01-01

he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

Multinationals' accountability on sustainability: the evolution of third-party assurance of sustainability reports

OpenAIRE

Perego, P.; Kolk, A.

2012-01-01

In this article we explore how multinational corporations (MNCs) adopt assurance practices to develop and sustain organizational accountability for sustainability. Using a panel of Fortune Global 250 firms over a period of 10 years, we document the diffusion patterns of third-party assurance of sustainability reports. We specifically investigate how evolving auditing practices, namely diversity of assurance standards and type of assurance providers, shape the quality of sustainability assuran...

Sustainable development in agriculture: is it really sustainable?

International Nuclear Information System (INIS)

Singh, S.R.K.; Srinivas, K.; Kumar, L.R.; Gupta, H.S.

2005-01-01

Indian agriculture has achieved remarkable success in the food grain production due to inception of 'rainbow revolution', which made the country self-sufficient in food production. Sustainable agriculture (SA) is an ongoing process, in which people take actions leading to development of agriculture that meets their current needs without compromising the ability of future generations to meet their needs. It advocates avoiding all those actions, which reduce the ability of future generations to meet out the present generations. It is based on the optimal interaction between clean environment, healthy economy, and vital society by avoiding trade-off of problems to other regions on to the future. Moreover, sustainable agriculture is the function of people's progress and nature's capacity. In fact, SA commits us to considering the long-term effect and to recognize our place within the ecosystem. It encourages a continuous reflection on the implications of human activity on the ecosystem. Empirical evidences shows that in the race of self-sufficiency in food grain production, we compromised a lot on social and environmental fronts. The aftermath of green revolution is not so sustainable as it showed reverse side too, in the form of environmental degradation and ecological imbalances. Such threats have led to the need for promoting sustainable development in agriculture. Due to several unsustainable activities which resulted in resource degradation in the form of top soil loss, ground water depletion and forest degradation. The average soil loss is estimated to be over 16 tonnes/ha/year. The ground water depletion resulted in several blocks as 'grey blocks' and 'dark blocks'. This happened mainly due to increase in number of tube-wells and free supply of electricity making the cost of pumping water very low. Rate of human induced land degradation is very high. Out of total geographical area of 329.0 million ha, 187 million ha (57.0 %) are reported to have degraded, of

Sustainability needs communication - German ICT-industry's strategy to promote sustainability

Energy Technology Data Exchange (ETDEWEB)

Tobias, M. [German Association for Information Technology, Telecommunications and New Media - BITKOM, Berlin (Germany); Pongratz, S. [Motorola Advanced Technology Center, Taunusstein (Germany)

2004-07-01

Information and communication technologies (ICT) lay the basis for the information society and have therefore a daily influence on almost everybody. This involves certain requirements regarding the purpose of a sustainable development as for example energy use, careful use of resources, and global compliance with social standards. However, ICT applications and their integration into business processes as well as daily private life also offer enormous potential for shaping sustainable development. Based on this realization, active companies and their associations are to play an important role in promoting new approaches for Sustainability. To this reason the German ICT-Association BITKOM together with some of the most active players in this field founded a new workgroup for International Environmental Policy and Sustainability. Main targets are the communication of an orientation towards sustainability within the own branch as well as the usage of ICT-products and services to enable sustainable development on a society basis. This covers political activities, publication of guidelines and brochures as well as the discussion of new approaches with scientists and NGOs. By critically questioning the approach within the own branch the process of a transparent communication shall be initiated, by which everybody will be able to contribute his specific part to the whole ''sustainability-puzzle''. (orig.)

Compendium of Environmental Sustainability Indicator Collections: 2005 Environmental Sustainability Index (ESI)

Data.gov (United States)

National Aeronautics and Space Administration — The 2005 Environmental Sustainability Index (ESI) portion of the Compendium of Environmental Sustainability Indicators Collection contains 103 variables for 146...

Navigating the sustainability landscape: a systematic review of sustainability approaches in healthcare.

Science.gov (United States)

Lennox, L; Maher, L; Reed, J

2018-02-09

Improvement initiatives offer a valuable mechanism for delivering and testing innovations in healthcare settings. Many of these initiatives deliver meaningful and necessary changes to patient care and outcomes. However, many improvement initiatives fail to sustain to a point where their full benefits can be realised. This has led many researchers and healthcare practitioners to develop frameworks, models and tools to support and monitor sustainability. This work aimed to identify what approaches are available to assess and influence sustainability in healthcare and to describe the different perspectives, applications and constructs within these approaches to guide their future use. A systematic review was carried out following PRISMA guidelines to identify publications that reported approaches to support or influence sustainability in healthcare. Eligibility criteria were defined through an iterative process in which two reviewers independently assessed 20% of articles to test the objectivity of the selection criteria. Data were extracted from the identified articles, and a template analysis was undertaken to identify and assess the sustainability constructs within each reported approach. The search strategy identified 1748 publications with 227 articles retrieved in full text for full documentary analysis. In total, 62 publications identifying a sustainability approach were included in this review (32 frameworks, 16 models, 8 tools, 4 strategies, 1 checklist and 1 process). Constructs across approaches were compared and 40 individual constructs for sustainability were found. Comparison across approaches demonstrated consistent constructs were seen regardless of proposed interventions, setting or level of application with 6 constructs included in 75% of the approaches. Although similarities were found, no approaches contained the same combination of the constructs nor did any single approach capture all identified constructs. From these results, a consolidated

The Sustainable Personality: Values and Behaviors in Individual Sustainability

Science.gov (United States)

Pappas, Jesse B.; Pappas, Eric C.

2015-01-01

Meaningful societal change begins with individual change. One cannot do for a community what one cannot do for one's self. The topic of Individual Sustainability is a controversial one, as students often appear to be unable to align their demonstrated behaviors with their admirable values related to sustainability. Individual behavior creates the…

Sustainable Sizing.

Science.gov (United States)

Robinette, Kathleen M; Veitch, Daisy

2016-08-01

To provide a review of sustainable sizing practices that reduce waste, increase sales, and simultaneously produce safer, better fitting, accommodating products. Sustainable sizing involves a set of methods good for both the environment (sustainable environment) and business (sustainable business). Sustainable sizing methods reduce (1) materials used, (2) the number of sizes or adjustments, and (3) the amount of product unsold or marked down for sale. This reduces waste and cost. The methods can also increase sales by fitting more people in the target market and produce happier, loyal customers with better fitting products. This is a mini-review of methods that result in more sustainable sizing practices. It also reviews and contrasts current statistical and modeling practices that lead to poor fit and sizing. Fit-mapping and the use of cases are two excellent methods suited for creating sustainable sizing, when real people (vs. virtual people) are used. These methods are described and reviewed. Evidence presented supports the view that virtual fitting with simulated people and products is not yet effective. Fit-mapping and cases with real people and actual products result in good design and products that are fit for person, fit for purpose, with good accommodation and comfortable, optimized sizing. While virtual models have been shown to be ineffective for predicting or representing fit, there is an opportunity to improve them by adding fit-mapping data to the models. This will require saving fit data, product data, anthropometry, and demographics in a standardized manner. For this success to extend to the wider design community, the development of a standardized method of data collection for fit-mapping with a globally shared fit-map database is needed. It will enable the world community to build knowledge of fit and accommodation and generate effective virtual fitting for the future. A standardized method of data collection that tests products' fit methodically

Sustainable Water Infrastructure

Science.gov (United States)

Resources for state and local environmental and public health officials, and water, infrastructure and utility professionals to learn about sustainable water infrastructure, sustainable water and energy practices, and their role.

Sustainability Statement and Policy

Science.gov (United States)

Journal of Education for Sustainable Development, 2009

2009-01-01

This article presents nine resources that focus on environmental education and sustainability. These include: (1) "Sustainability Statement and Policy," Dalhousie University, Nova Scotia, Canada, 2009, which is available at http://office.sustainability.dal.ca/Governance; (2) "Climate Literacy: The Essential Principles of Climate…

Sustainability Annual Report 2013

OpenAIRE

2013-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2014

OpenAIRE

2014-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2017

OpenAIRE

2017-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2011

OpenAIRE

2011-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2012

OpenAIRE

2012-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2015

OpenAIRE

2015-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Sustainability Annual Report 2016

OpenAIRE

2016-01-01

Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

Biorefinery Sustainability Analysis

DEFF Research Database (Denmark)

J. S. M. Silva, Carla; Prunescu, Remus Mihail; Gernaey, Krist

2017-01-01

This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system and of t......This chapter deals with sustainability analysis of biorefinery systems in terms of environmental and socio-economic indicators . Life cycle analysis has methodological issues related to the functional unit (FU), allocation , land use and biogenic carbon neutrality of the reference system...... and of the biorefinery-based system. Socio-economic criteria and indicators used in sustainability frameworks assessment are presented and discussed. There is not one single methodology that can aptly cover the synergies of environmental, economic, social and governance issues required to assess the sustainable...

Sustainable Enterprise Excellence

DEFF Research Database (Denmark)

Edgeman, Rick

2013-01-01

Structured Abstract Purpose: Sustainable Enterprise Excellence (SEE) is defined and developed through integration and expansion of business excellence modeling and sustainability thought. The intent is to enable simple yet reliable enterprise assessment of triple bottom line (TBL) performance...... and produce actionable enterprise foresight that can enable next best practices and sources of sustainable competitive advantage through innovation. Methodology: Key elements of SEE are identified from various business excellence and sustainability reporting sources, including the Global Reporting Initiative...... assessment approach similar in structure to those behind established excellence awards are developed that enable enterprise assessment of progress toward SEE. The resulting assessment is delivered in a highly consumable, combined narrative and graphic format referred to as a SEE NEWS Report. Practical...

TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma.

Science.gov (United States)

Deng, Zheng-Hao; Cao, Hui-Qiu; Hu, Yong-Bin; Wen, Ji-Fang; Zhou, Jian-Hua

2011-01-01

We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway. © 2010 The Authors. APMIS © 2010 APMIS.

Advancing a sustainable highway system : highlights of FHWA sustainability activities

Science.gov (United States)

2014-06-01

FHWA is undertaking a significant amount of work related to sustainability across a number of program areas throughout the Agency. The purpose of this report is to showcase some of the ways in which FHWA is incorporating and embedding sustainability ...

What is sustainability economics?

Energy Technology Data Exchange (ETDEWEB)

Baumgaertner, Stefan [Department of Sustainability Sciences, Leuphana University of Lueneburg (Germany); Department of Economics, Leuphana University of Lueneburg (Germany); Quaas, Martin [Department of Economics, University of Kiel (Germany)

2010-01-15

While economists have been contributing to the discussion of various aspects of sustainability for decades, it is just recently that the term 'sustainability economics' was used explicitly in the ecological, environmental, and resource economics community. Yet, the contributions that use the term 'sustainability economics' do not refer to any explicit definition of the term, and are not obviously joined by common or unifying characteristics, such as subject focus, methodology, or institutional background. The question thus arises: what is 'sustainability economics'? In this essay, we systematically define and delineate 'sustainability economics' in terms of its normative foundation, aims, subject matter, ontology, and genuine research agenda. (author)

Deliverable 2 (SustainAQ)

NARCIS (Netherlands)

Schneider, O.; Julian, B.; Bosman, R.; Eding, E.

2009-01-01

The European Project SustainAQ (Framework 6) aims to identify the limiting factors for the sustainable production of aquatic origin food in Eastern Europe. It focuses on the possible use of Recirculation Aquaculture Systems (RAS) as sustainable method for the production of aquatic animals as

Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

International Nuclear Information System (INIS)

Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

2009-01-01

Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H 2 O 2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H 2 O 2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H 2 O 2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

Market solutions for sustainable cities

NARCIS (Netherlands)

Ursem, Thomas; Nijkamp, Peter

1995-01-01

Sustainable development has become a globally accepted policy objective. It is however, increasingly recognized that the implementation of sustainability strategies has to take place at a decentralized level. This has also provoked the idea of urban sustainability. The notion of sustainable city is

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

Directory of Open Access Journals (Sweden)

Lescaille Géraldine

2012-03-01

Full Text Available Abstract Backgrounds An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC progression. Methods Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. Results OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Conclusions Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.

Science.gov (United States)

Lescaille, Géraldine; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste; Mourah, Samia

2012-03-23

An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity

International Nuclear Information System (INIS)

Bajaj, Bharat G.; Verma, Subhash C.; Lan, Ke; Cotter, Murray A.; Woodman, Zenda L.; Robertson, Erle S.

2006-01-01

Pim kinases are proto-oncogenes that are upregulated in a number of B cell cancers, including Epstein-Barr Virus (EBV) associated Burkitt's lymphoma. They have also been shown to be upregulated in Kaposi sarcoma-associated herpes virus (KSHV) infected primary B cells. Most cells in KSHV-associated tumors are latently infected and express only a small subset of viral genes, with KSHV latency associated nuclear antigen (LANA) being constitutively expressed. LANA regulates the transcription of a large number of cellular and viral genes. Here, we show that LANA upregulates transcription from the Pim-1 promoter (pPim-1) and map this activation to a region in the promoter located within the sequence (-681 to +37). We show that LANA expressing cells can proliferate faster and are better protected from drug induced apoptosis. Since transition through cell cycle check points and anti-apoptosis are functions associated with Pim-1, it is likely that higher Pim-1 expression in cells expressing LANA is responsible, at least in part, for this effect. A Pim-1 phosphorylation site was also identified within the amino-terminal domain of LANA. Using in vitro kinase assays, we confirmed that LANA was indeed a Pim-1 substrate, and the failure of Pim-1 to phosphorylate LANA mutated at SS205/6RR identified this site as the specific serine residues phosphorylated by Pim-1. This report provides valuable insight into yet another cellular signaling pathway subverted by KSHV LANA and suggests a contribution to KSHV related oncogenesis

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

International Nuclear Information System (INIS)

Lescaille, Géraldine; Mourah, Samia; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste

2012-01-01

An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion

Sustainable winegrowing: current perspectives

Directory of Open Access Journals (Sweden)

Mariani A

2015-05-01

Full Text Available Angela Mariani,1 Antonella Vastola2 1Department of Economic and Legal Studies, University Parthenope, Naples, 2School of Agricultural, Forestry, Food and Environmental Sciences, University of Basilicata, Potenza, Italy Abstract: The winegrowing sector worldwide is strongly committed to improving environmental and social sustainability. The aim of this work, based on a literature review, is to highlight current sustainability perspectives and the related main issues. There is a broad consensus that the challenge to achieve a greater spread of sustainable practices is to enhance environmental and social sustainability while maintaining economic viability. From the producers' point of view, the priority is to bridge the still substantial knowledge gaps in terms of perceived environmental benefits, economic benefits, and costs. Thus, an increased research effort focusing on the costs and benefits of different winegrowing practices and technical assistance with implementation might support their diffusion. Moreover, targeted marketing strategies are needed to: enhance consumers' involvement and their attitude toward sustainable wine; improve understanding and use of sustainable labels and claims; and raise awareness of some environmental credentials of wine packaging, mainly with reference to lightweight glass bottles. Keywords: winegrower, sustainability, wine, consumer, marketing strategies

Using Sustainability Metrics and Indicators to Design Sustainable Supply Chains

Science.gov (United States)

Sustainability is widely associated with the statement from the World Commission on Environment and Development, 1987: “… development that meets the needs of the present without compromising the ability of future generations to meet their own needs…” Hence, sustainability is abo...

Educating Professionals for Sustainable Futures

Directory of Open Access Journals (Sweden)

Hille Janhonen-Abruquah

2018-02-01

Full Text Available The recent discourse on sustainability science calls for interdisciplinary research. The home economics science approach ranges from individual actions to the involvement of communities and societies at large, and thus it can provide important perspectives on cultural sustainability. The aim of the research is to study the linkage between cultural sustainability and service sector education to support the creation of sustainable professions. In the present small-scale empirical study, the food service degree curriculum of a Finnish vocational college and teachers’ group interview data were analyzed to find how cultural sustainability is presented in the curriculum and how it is understood by teachers and integrated into teaching practices. Previous cultural sustainability research identifies four perspectives of cultural sustainability: (1 vitality of cultural traditions; (2 economic starting point; (3 diversity together with maintenance of local culture; and (4 possible influence on the balance between human actions and environment. Findings indicate that sustainability, including cultural sustainability, is integrated in the curriculum and considered important by teachers. Translating these into practice remains a challenge. The balance between human and nature was mostly understood as recycling, use of public transport, sustainable consumption, and taking trips to the nature nearby. Cultural sustainability as a concept is not well known, although themes such as multicultural issues, equality, charity, and environmental responsibility were included in teachers’ practical lessons daily. Feasts and celebrations in learning were opportunities to view cultural sustainability widely. This paper provides a way forward for the teachers to develop further their pedagogical practices.

The joint discourse 'reflexive sustainable development'. From weak towards strong sustainable development

International Nuclear Information System (INIS)

Nilsen, Heidi Rapp

2010-01-01

The purpose of this paper is to contribute towards moving the predominant situation of weak sustainable development (WSD) in the direction of strong sustainable development (SSD). More people - academics, politicians, bureaucrats and laymen alike - need to recognize SSD as an alternative to WSD. A joint discourse of WSD and SSD is suggested, called reflexive sustainable development. Here, advocates of WSD and SSD must argue for each specific case why their solution is better. This will expose, amongst other things, the ethical foundations which form part of resulting policy advice. Reflexive sustainable development is to be framed in discourse ethics, thereby remedying the power imbalance and allowing for substantial discussion. Reflexive sustainable development builds on a common theoretical base but will not lead to consensus in all matters. A family metaphor is introduced to inspire a discourse of both consensus and compromise. (author)

"Facilitated" amino acid transport is upregulated in brain tumors.

Science.gov (United States)

Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

1998-05-01

The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary

Engineering students' sustainability approaches

Science.gov (United States)

Haase, S.

2014-05-01

Sustainability issues are increasingly important in engineering work all over the world. This article explores systematic differences in self-assessed competencies, interests, importance, engagement and practices of newly enrolled engineering students in Denmark in relation to environmental and non-environmental sustainability issues. The empirical base of the article is a nation-wide, web-based survey sent to all newly enrolled engineering students in Denmark commencing their education in the fall term 2010. The response rate was 46%. The survey focused on a variety of different aspects of what can be conceived as sustainability. By means of cluster analysis, three engineering student approaches to sustainability are identified and described. The article provides knowledge on the different prerequisites of engineering students in relation to the role of sustainability in engineering. This information is important input to educators trying to target new engineering students and contribute to the provision of engineers equipped to meet sustainability challenges.

Sustainability at BPA 2013

Energy Technology Data Exchange (ETDEWEB)

None

2013-12-01

THIS IS THE THIRD YEAR BPA has reported on sustainability program accomplishments. The report provides an opportunity to review progress made on sustainability initiatives, evaluate how far we have come and how much we can improve. The program has demonstrated maturation as the concepts of sustainability and resource conservation are communicated and understood. The sustainability program started as an employee-driven “grass roots” effort in 2010. Sustainability is becoming a consideration in how work is performed. The establishment of several policies supporting sustainability efforts proves the positive progress being made. In 2009, BPA became a founder and member of The Climate Registry, a nonprofit collaboration that sets standards to calculate, verify and report greenhouse gas emissions. This year, BPA completed and published our Greenhouse Gas inventory for the years of 2009, 2010 and 2011. The 2012 inventory is currently in the process of third-party verification and scheduled for public release in January 2014. These inventories provide a concrete measure of the progress we are making.

Sustainability in Electricity Markets. Study for the Dutch Transition Platform on Sustainable Electricity

International Nuclear Information System (INIS)

2005-12-01

The current energy system is not sustainable. This situation is liable to lead to serious and costly consequences in the long term. The two most important themes to be addressed are climate change and securing energy supplies, particularly in view of the increasing dependency on fossil fuels from geo-politically unstable regions. That is why the Dutch government has decided to strive for a transition towards a Sustainable Energy System. The aim of the energy transition is to transform the current energy system over the coming decades into a sustainable energy system. The participants in this Energy Transition have established six themes for achieving a sustainable energy economy within 50 years. Within these themes experiments are being conducted, experiments that ensure that the final aims become clearer and feasible. Market participants, scientific and civil organizations, and government agencies are taking the lead in each of the six themes: (a) Green raw materials; (b) Sustainable Mobility; (c) Chain Efficiency; (d) New Gas; (e) Sustainable Electricity; (f) Energy in the built environment. This document provides input for the theme on Sustainable Electricity. The Dutch Ministry of Economic Affairs together with SenterNovem is preparing a Platform Renewable Electricity Supply. In this Platform representatives from different stakeholders are to take part. The platform is meant to stimulate concrete actions/initiatives towards sustainable electricity supply. SenterNovem has asked PricewaterhouseCoopers (PwC) to make an international inventory of electricity market developments, with a focus on the impact for future sustainable electricity supply. The question which options for electricity generation are the most suitable for a sustainable electricity supply will be dealt with by KEMA (a Dutch research institute for the electric power industry)

NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

International Nuclear Information System (INIS)

Chen, Zhi-Dong; Xu, Liang; Tang, Kan-Kai; Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong; Sun, Ren-Hua; Mo, Shi-Jing

2016-01-01

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhi-Dong [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Xu, Liang [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Tang, Kan-Kai [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Sun, Ren-Hua, E-mail: jqin168@hotmail.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Mo, Shi-Jing, E-mail: msj860307@163.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China)

2016-09-10

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

Sustainable IT and IT for Sustainability

Science.gov (United States)

Liu, Zhenhua

Energy and sustainability have become one of the most critical issues of our generation. While the abundant potential of renewable energy such as solar and wind provides a real opportunity for sustainability, their intermittency and uncertainty present a daunting operating challenge. This thesis aims to develop analytical models, deployable algorithms, and real systems to enable efficient integration of renewable energy into complex distributed systems with limited information. The first thrust of the thesis is to make IT systems more sustainable by facilitating the integration of renewable energy into these systems. IT represents the fastest growing sectors in energy usage and greenhouse gas pollution. Over the last decade there are dramatic improvements in the energy efficiency of IT systems, but the efficiency improvements do not necessarily lead to reduction in energy consumption because more servers are demanded. Further, little effort has been put in making IT more sustainable, and most of the improvements are from improved "engineering" rather than improved "algorithms". In contrast, my work focuses on developing algorithms with rigorous theoretical analysis that improve the sustainability of IT. In particular, this thesis seeks to exploit the flexibilities of cloud workloads both (i) in time by scheduling delay-tolerant workloads and (ii) in space by routing requests to geographically diverse data centers. These opportunities allow data centers to adaptively respond to renewable availability, varying cooling efficiency, and fluctuating energy prices, while still meeting performance requirements. The design of the enabling algorithms is however very challenging because of limited information, non-smooth objective functions and the need for distributed control. Novel distributed algorithms are developed with theoretically provable guarantees to enable the "follow the renewables" routing. Moving from theory to practice, I helped HP design and implement

The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

International Nuclear Information System (INIS)

Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli; Zhang, Xiaodong; Ye, Lihong

2013-01-01

Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-κB through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

Directory of Open Access Journals (Sweden)

Saravanabavan Sayanthooran

2016-01-01

Full Text Available Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC, glutathione S-transferase mu 1 (GSTM1, glucose-6-phosphate dehydrogenase (G6PD, fibroblast growth factor-23 (FGF23, and NLR family pyrin domain containing 3 (NLRP3. Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR was carried out for the selected populations: CKDu patients (n=43, chronic kidney disease patients (CKD; n=14, healthy individuals from a CKDu endemic area (GHI; n=9, and nonendemic area (KHI; n=16. Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI (p=0.000. GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold (p<0.05. Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed (p<0.01, with greater fold changes in CKD. Conclusion. Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions.

The oncoprotein HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote the proliferation of breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yingyi; Zhao, Yu; Li, Leilei; Shen, Yu; Cai, Xiaoli [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong, E-mail: yelihong@nankai.edu.cn [Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2013-05-03

Highlights: •HBXIP is able to upregulate the expression of PDGFB in breast cancer cells. •HBXIP serves as a coactivator of activating transcription factor Sp1. •HBXIP stimulates the PDGFB promoter via activating transcription factor Sp1. •HBXIP promotes the proliferation of breast cancer cell via upregulating PDGFB. -- Abstract: We have reported that the oncoprotein hepatitis B virus X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. Previously, we showed that HBXIP was able to activate nuclear factor-κB (NF-κB) in breast cancer cells. As an oncogene, the platelet-derived growth factor beta polypeptide (PDGFB) plays crucial roles in carcinogenesis. In the present study, we found that both HBXIP and PDGFB were highly expressed in breast cancer cell lines. Interestingly, HBXIP was able to increase transcriptional activity of NF-κB through PDGFB, suggesting that HBXIP is associated with PDGFB in the cells. Moreover, HBXIP was able to upregulate PDGFB at the levels of mRNA, protein and promoter in the cells. Then, we identified that HBXIP stimulated the promoter of PDGFB through activating transcription factor Sp1. In function, HBXIP enhanced the proliferation of breast cancer cells through PDGFB in vitro. Thus, we conclude that HBXIP upregulates PDGFB via activating transcription factor Sp1 to promote proliferation of breast cancer cells.

Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

Directory of Open Access Journals (Sweden)

John M McPartland

Full Text Available The "classic" endocannabinoid (eCB system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA and 2-arachidonoylglycerol (2-AG, and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis also modulate the eCB system.Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia.

Science.gov (United States)

Labib, Hany Abedelmalik; Elantouny, Neveen G; Ibrahim, Nevin F; Alnagar, Ahmed A

2017-08-01

Many studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is upregulated in tumor tissue. However, its association with B-cell acute lymphoblastic leukemia (B-ALL) remains poorly understood. The expression of miR-21 was detected by real-time quantitative PCR in 75 children with de novo B-ALL as well as in 50 healthy controls. This study was conducted to evaluate the miR-21 as a biomarker for risk assessment, diagnosis and prognosis. Compared with normal controls, miR-21 expression was significantly upregulated in childhood B-ALL patients. Using the receiver operating characteristic curve 3.23 was selected as the cut-off value of miR-21 expression in distinguishing patients from controls. Patients group with High miR-21 expression was significantly associated with those aged 10 years, lower platelets count, more incidence of CNS infiltration and poorer treatment outcome also, they showed a significantly poorer disease-free survival (DFS) and overall survival (OS) compared to those with low miR-21 expression group. Its expression was an independent prognostic marker according to multivariate analysis. This is the first report demonstrating the upregulation of miR-21 in childhood B-ALL, and its association with poor response to induction therapy, shorter DFS and OS. These results suggest that miR-21 upregulation represent an unfavorable prognostic marker in Childhood B-ALL.

Digital sustainability: basic conditions for sustainable digital artifacts and their ecosystems

OpenAIRE

Stürmer, Matthias; Abu-Tayeh, Gabriel; Myrach, Thomas

2017-01-01

The modern age has heralded a shift from the industrial society, in which natural resources are crucial input factors for the economy, towards a knowledge society. To date, sustainability literature has treated knowledge—and in particular digital artifacts—mainly as a means to the end of achieving sustainable development. In this conceptual paper, we argue that digital artifacts themselves ought also to be considered as resources, which also need to be sustainable. While over-consumption is a...

Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells.

Science.gov (United States)

Batman, Gavin; Oliver, Anthony W; Zehbe, Ingeborg; Richard, Christina; Hampson, Lynne; Hampson, Ian N

2011-01-01

We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used. Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression. These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug's selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

Directory of Open Access Journals (Sweden)

Katherine R Cronin

Full Text Available BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001 at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Managing Sustainability in Fruit Production

OpenAIRE

Taragola, N.; Van Passel, S.; Zwiekhorst, W.

2012-01-01

As fruit growers are faced with a growing need for sustainable development, it is important to integrate sustainability into their management processes. This research applies and evaluates a self-analysis tool for entrepreneurs called the ‘sustainability scan’. The scan identifies 23 sustainability themes, divided according to the 3P-framework (People, Planet and Profit). In the scan, it is assumed that the management of these themes is at the core of sustainable entrepren...

Sustainable Building Operation

DEFF Research Database (Denmark)

Jensen, Jesper Ole

2009-01-01

of sustainable building operation and a survey amongst building administrators from the private and the social housing sector. Our results show that there are many good examples on sustainable building operation in Danish housing estates, where local building managers, residents etc. have gained impressive......Energy-savings in the existing building stock have becomes a main goal in national and international policies. Often focus is on building-renovations, whereas the potential of sustainable building operation to a large extent has been neglected. Nevertheless, international research as well...... as practical experiences from Danish housing estates indicates that there are large potentials for energy savings by focusing on the operation of the buildings. We suggest that in order to achieve sustainability in the existing housing, renovation and operations should be seen as integrated parts...

Sustainable intensification of agriculture for human prosperity and global sustainability

NARCIS (Netherlands)

Rockstrom, J.; Williams, J.; Daily, G.; Noble, A.; Matthews, N.; Gordon, L.; Wetterstrand, H.; DeClerck, F.; Fraiture, de C.M.S.

2017-01-01

There is an ongoing debate on what constitutes sustainable intensification of agriculture (SIA). In this paper, we propose that a paradigm for sustainable intensification can be defined and translated into an operational framework for agricultural development. We argue that this paradigm must now be

Exercise training attenuated chronic cigarette smoking-induced up-regulation of FIZZ1/RELMα in lung of rats.

Science.gov (United States)

Ma, Wan-li; Cai, Peng-cheng; Xiong, Xian-zhi; Ye, Hong

2013-02-01

FIZZ/RELM is a new gene family named "found in inflammatory zone" (FIZZ) or "resistin-like molecule" (RELM). FIZZ1/RELMα is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ1/RELMα expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsiveness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyperresponsiveness and up-regulation of FIZZ1/RELMα, rat chronic cigarette smoking model was established. The rats were treated with regular exercise training and their airway responsiveness was measured. Hematoxylin and eosin (HE) staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMα. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMα, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMα induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

At Home with Sustainability: From Green Default Rules to Sustainable Consumption

Directory of Open Access Journals (Sweden)

Lara Anne Hale

2018-01-01

Full Text Available Although it is often assumed that default rules affect change without awareness, this paper suggests that contrast with the default and transition into conscious adoption of the default design may be the starting point to establish long-term changes in consumer behavior. Despite the rooting of default rules in subconscious decision-making, this research finds that, ultimately, awareness drives the demand necessary for the creation of sustainable consumption. Whereas direct appeal to individuals has a disappointing level of influence on sustainability choices, it is understood that green consumers do come from somewhere. Green default rules offer interesting prospects for sidestepping the drawbacks of direct marketing to individuals. Under green default rules, behavior is guided by a default, such as utilities automatically sending customers renewables-sourced instead of fossil-fuel-based energy. To act otherwise requires additional effort and is less likely. Motivated by a need to understand how defaults might bridge standards and sustainable consumption, I investigate how organizational processes potentially lead from standardized green default rules to individual awareness that can spread and facilitate sustainable consumption. This paper examines the Active House sustainable building demonstrations in Europe in order to understand how (1 communications and market creation and (2 responsible, user-centered experimentation are organized to move from defaults to sustainable consumption.

Utrophin up-regulation by an artificial transcription factor in transgenic mice.

Directory of Open Access Journals (Sweden)

Elisabetta Mattei

2007-08-01

Full Text Available Duchenne Muscular Dystrophy (DMD is a severe muscle degenerative disease, due to absence of dystrophin. There is currently no effective treatment for DMD. Our aim is to up-regulate the expression level of the dystrophin related gene utrophin in DMD, complementing in this way the lack of dystrophin functions. To this end we designed and engineered several synthetic zinc finger based transcription factors. In particular, we have previously shown that the artificial three zinc finger protein named Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from the utrophin promoter "A". Here we report on the characterization of Vp16-Jazz-transgenic mice that specifically over-express the utrophin gene at the muscular level. A Chromatin Immunoprecipitation assay (ChIP demonstrated the effective access/binding of the Jazz protein to active chromatin in mouse muscle and Vp16-Jazz was shown to be able to up-regulate endogenous utrophin gene expression by immunohistochemistry, western blot analyses and real-time PCR. To our knowledge, this is the first example of a transgenic mouse expressing an artificial gene coding for a zinc finger based transcription factor. The achievement of Vp16-Jazz transgenic mice validates the strategy of transcriptional targeting of endogenous genes and could represent an exclusive animal model for use in drug discovery and therapeutics.

Green innovation and sustainable industrial systems within sustainability and company improvement perspective

Science.gov (United States)

Edi Nugroho Soebandrija, Khristian

2017-12-01

This paper comprises discussion of Green Innovation and Sustainable Industrial Systems within Sustainability and Company Improvement Perspective of beverage manufacturing company (BMC). The stakeholder theory is the grand theory for the company improvement perspective in this paper. The data processing in this paper is conducted through software which are SEM-PLS with SmartPLS 2.0 and SPSS 19. The specified objective of this paper has focus on sustainability as one of 6 variables, in lieu of those 6 variables as the big picture. The reason behind this focus on sustainability is the fact that there are assorted challenges in sustainability that is ranging from economic, environment and company perspectives. Those challenges in sustainability include the sustainable service supply chain management and its involvement of society. The overall objective is to analyze relationship hypothesis of 6 variables, 4 of them (leadership, organizational learning, innovation, and performance) are based on Malcolm Baldrige’s performance excellence concept to achieve sustainability and competitive advantage through company-competitor and customer questionnaire, and its relation to Total Quality Management (TQM) and Quality Management System (QMS). In conclusion, the spearheaded of company improvement in this paper is in term of consumer satisfaction through 99.997% quality standards. These can be achieved by ambidexterity through exploitation and exploration innovation. Furthermore, in this paper, TQM enables to obtain popularity brand index achievement that is greater than 45.9%. Subsequently, ISO22000 of food security standard encompasses quality standard of ISO9000 and HACCP. Through the ambidexterity of exploitation and exploration (Non Standard Product Inspection) NOSPI machine, the company improvement generates the achievement of 75% automation, 99.997% quality control standard and 80% of waste reduction.

Specificities of sustainable tourism planning

Directory of Open Access Journals (Sweden)

Jegdić Vaso

2013-01-01

Full Text Available In the past two decades, companies have been mentioning achievement of sustainability in their activities as a target of companies, governments and non-profit organizations, although measuring the degree to which an organization conducts its activities in a sustainable manner, can be very difficult. Sustainable tourism development requires a process of planning and management that will unite the interests of various stakeholders in a sustainable and strategic way. It requires an understanding of the meaning of sustainable development and guiding values for promoting sustainable tourism. The paper points to the importance of cross-sector partnerships and the roles of different stakeholders in the planning of sustainable tourism projects. Special importance is given to the community of which a willingness to understand the impacts of tourism industry is expected, as well as various procedures of engagement in participatory planning, consensus building and conflict resolution among all stakeholders. The aim of this research is to find an optimal model of planning of sustainable tourism projects that would take into consideration the interests of all stakeholders and reflect the specificities imposed by the acceptance of the concept of sustainable development by all participants in the project.

THE CORRELATION BETWEEN SUSTAINABLE PERFORMANCE MEASURES AND ORGANIZATIONAL SUSTAINABILITY IN THE BRAZILIAN CONTEXT

Directory of Open Access Journals (Sweden)

RODRIGO GOYANNES GUSMÃO CAIADO

2016-12-01

Full Text Available Over the past few years, issues of sustainability are gaining greater prominence among organizations and their stakeholders around the world and with it the effective measurement of environmental performance has been a challenge for sustainable transition. The purpose of the article is to analyse, through the the perception of market experts and researchers, what sustainable performance measures have stronger positive correlation to achieve organizational sustainability in order to help employees in making decisions that reduce the consumption of resources and that create value throughout its chain. The research is of an exploratory and descriptive nature, with qualitative and quantitative method and has a deductive logic. It aims to help professionals and academics who want to start the measurement and continuous improvement of economic, environmental, social, governance and technical performance of their organizations. Finally, the analyzes allow direct efforts to sustainable measures considered most important, allowing the transition of the organization for sustainability.

The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

International Nuclear Information System (INIS)

Vu, Hoang Anh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

2009-01-01

We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.

Action Research for Sustainability

DEFF Research Database (Denmark)

Egmose, Jonas

on urban sustainability the need to move towards sustainability at societal level is conceptualised as a democratic challenge questioning the way we live on planet earth. By understanding sustainability as an immanent and emergent ability of ecological and social life, continuously to renew itself without...... with a greater say in the future of urban sustainability research, the work shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia, where aspects...

Action Research for Sustainability

DEFF Research Database (Denmark)

Egmose, Jonas

by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...

Appendix 1：Upregulated genes in gene expression profile （P<0.05 ...

Indian Academy of Sciences (India)

lazi

Appendix 1: Upregulated genes in gene expression profile«P2）. Probe_s. Gene_Symbol pvalues foldchange. Probe_S. et_ID. Gene_Symbol pvalues foldchange. et_ID. 1370355. 1393751. Scd1. 1.35E-04. 25.77. Loc1009122508.06E-03. 2.55. -at at. 1398250. 1370870. Acot1. 2.43E-02. 12.18. Me1.

Sustainable Agricultural Marketing Initiatives

Directory of Open Access Journals (Sweden)

Hakan Adanacıoğlu

2015-07-01

Full Text Available Sustainable marketing is a holistic approach that puts equal emphasis on environmental, social equity, and economic concerns in the development of marketing strategies. The purpose of the study is to examine and discuss the sustainable agricultural marketing initiatives practiced throughout the World and Turkey, and to put forth suggestions to further improve the performance of agricultural marketing initiatives in Turkey. Some of the sustainable agricultural marketing initiatives practiced around the world are carried out through civil organizations. Furthermore; some of these initiatives have also launched by farmers, consumers, food processors and retailers. The long-term strategies to increase these initiatives should be determined due to the fact that examples of successful sustainable agricultural marketing initiatives are inadequate and cannot be spread in Turkey. In this context, first of all, the supports provided by the government to improve agricultural marketing systems, such as EU funds for rural development should be compatible with the goals of sustainable marketing. For this purpose, it should be examined whether all proposed projects related to agricultural marketing meet the social, economic, and environmental principles of sustainable marketing. It is important that supporting organizations, especially civil society organisations, should take an active role for faster dissemination and adoption of sustainable agricultural marketing practices in Turkey. These organizations may provide technical assistance in preparing successful project proposals and training to farm groups. In addition, the other organizations, such as local administrations, producers' associations, cooperatives, can contribute to the success of sustainable agricultural marketing initiatives. The use of direct marketing strategies and vertical integration attempts in sustainable agricultural marketing initiatives that will likely be implemented in Turkey is

Sustainability Reporting for Start ups:Recommendations for customized Instruments to promote Sustainability

OpenAIRE

Schäfer, Barbara

2015-01-01

Sustainable development can be enforced by external interventions, such as laws and regulations. Sustainability research however finds that innovation, often emerging in the form of entrepreneurship, has the largest potential to contribute to sustainable development.Entrepreneurship is considered an important driver of economic growth, job creation and productivity. New businesses show innovative and creative potential to replace old products and to contribute to quality of life improvements....

A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions

DEFF Research Database (Denmark)

Nielsen, Carsten Uhd; Rasmussen, Rune N; Mo, Junying

2016-01-01

Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions...... in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect...... of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could...

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

Science.gov (United States)

Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

Biofuels and sustainability.

Science.gov (United States)

Solomon, Barry D

2010-01-01

Interest in liquid biofuels production and use has increased worldwide as part of government policies to address the growing scarcity and riskiness of petroleum use, and, at least in theory, to help mitigate adverse global climate change. The existing biofuels markets are dominated by U.S. ethanol production based on cornstarch, Brazilian ethanol production based on sugarcane, and European biodiesel production based on rapeseed oil. Other promising efforts have included programs to shift toward the production and use of biofuels based on residues and waste materials from the agricultural and forestry sectors, and perennial grasses, such as switchgrass and miscanthus--so-called cellulosic ethanol. This article reviews these efforts and the recent literature in the context of ecological economics and sustainability science. Several common dimensions for sustainable biofuels are discussed: scale (resource assessment, land availability, and land use practices); efficiency (economic and energy); equity (geographic distribution of resources and the "food versus fuel" debate); socio-economic issues; and environmental effects and emissions. Recent proposals have been made for the development of sustainable biofuels criteria, culminating in standards released in Sweden in 2008 and a draft report from the international Roundtable on Sustainable Biofuels. These criteria hold promise for accelerating a shift away from unsustainable biofuels based on grain, such as corn, and toward possible sustainable feedstock and production practices that may be able to meet a variety of social, economic, and environmental sustainability criteria.

Sustainable Consumption Dilemmas

Directory of Open Access Journals (Sweden)

Kees Vringer

2017-06-01

Full Text Available To examine which considerations play a role when individuals make decisions to purchase sustainable product varieties or not, we have conducted a large scale field experiment with more than 600 participating households. Households can vote on whether the budgets they receive should only be spent on purchasing the sustainable product variety, or whether every household in a group is free to spend their budget on any product variety. By conducting several treatments, we tested whether people tend to view sustainable consumption as a social dilemma or as a moral dilemma. We find little support for the hypothesis that social dilemma considerations are the key drivers of sustainable consumption behaviour. Participants seem to be caught in a moral dilemma in which they not only weigh their individual financial costs with the sustainable benefits but they also consider the consequences of restricting other people’s freedom of choice. Complementary survey results further substantiate this claim and show that many people are reluctant to impose restrictions on their peers, but, at the same time, our results also suggest substantial support for the government to regulate the availability of unsustainable product varieties.

Subarachnoid hemorrhage-induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

DEFF Research Database (Denmark)

Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Xu, Cang-Bao

2003-01-01

experimental SAH. METHODS: Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive...... RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. CONCLUSIONS: Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH...... to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm....

Sustaining Participatory Design Initiatives

DEFF Research Database (Denmark)

Iversen, Ole Sejer; Dindler, Christian

2014-01-01

While many participatory design (PD) projects succeed in establishing new organisational initiatives or creating technology that is attuned to the people affected, the issue of how such results are sustained after the project ends remains an important challenge. We explore the challenge...... these various forms of sustainability may be pursued in PD practice and how they can become a resource in reflecting on PD activities. Finally, we discuss implications for PD practice, suggesting that a nuanced conception of sustainability and how it may relate to PD practice are useful resources for designers...... of sustaining PD initiatives beyond the individual project and discuss implications for PD practice. First, based on current PD literature, we distinguish between four ideal typical forms of sustainability: maintaining, scaling, replicating and evolving. Second, we demonstrate from a case study how...

Sustainable Process Synthesis-Intensification

DEFF Research Database (Denmark)

Babi, Deenesh Kavi; Holtbruegge, Johannes; Lutze, Philip

2014-01-01

Sustainable process design can be achieved by performing process synthesis and process intensification together. This approach first defines a design target through a sustainability analysis and then finds design alternatives that match the target through process intensification. A systematic......, multi-stage framework for process synthesis- intensification that identifies more sustainable process designs has been developed. At stages 1-2, the working scale is at the level of unit operations, where a base case design is identified and analyzed with respect to sustainability metrics. At stages 3......, a phenomena-based process synthesis method is applied, where the phenomena involved in each tasks are identified, manipulated and recombined to generate new and/or existing unit operations configured into flowsheets that are more sustainable from those found in the previous levels. An overview of the key...

Teaching sustainable design

Energy Technology Data Exchange (ETDEWEB)

Cooper, P.; Haggard, K.; Knuckles, A.; Le Noble, J. [California Polytechnic State Univ., San Luis Obispo, CA (United States)

1995-11-01

Sustainable design is inclusive, holistic and integrative. It require humility and guts, caring and a certain degree of stubbornness. It helps to do it cooperatively in a group. Human interest in sustainability has gained a great deal of impetus over the last several years as the problems of the late 20th and the early 21st century have become clearer. Design for sustainability broadens and integrates many previously separate design concerns to create a unified approach that is both compelling and ripe with new possibilities. Ecosystem regeneration, ecological land use planning, biometric design, regional environmental and economic viability, natural landscape maintenance, resource optimization, integrated infrastructure system, neotraditional and pedestrian oriented urban design, passive solar architecture, appropriate technology, renewable building materials, healthy buildings, and the aesthetics of place; are a few of these design concerns that, when welded together, can create sustainability.

A Bivalent Securinine Compound SN3-L6 Induces Neuronal Differentiation via Translational Upregulation of Neurogenic Transcription Factors

Directory of Open Access Journals (Sweden)

Yumei Liao

2018-04-01

Full Text Available Developing therapeutic approaches that target neuronal differentiation will be greatly beneficial for the regeneration of neurons and synaptic networks in neurological diseases. Protein synthesis (mRNA translation has recently been shown to regulate neurogenesis of neural stem/progenitor cells (NSPCs. However, it has remained unknown whether engineering translational machinery is a valid approach for manipulating neuronal differentiation. The present study identifies that a bivalent securinine compound SN3-L6, previously designed and synthesized by our group, induces potent neuronal differentiation through a novel translation-dependent mechanism. An isobaric tag for relative and absolute quantitation (iTRAQ-based proteomic analysis in Neuro-2a progenitor cells revealed that SN3-L6 upregulated a group of neurogenic transcription regulators, and also upregulated proteins involved in RNA processing, translation, and protein metabolism. Notably, puromycylation and metabolic labeling of newly synthesized proteins demonstrated that SN3-L6 induced rapid and robust activation of general mRNA translation. Importantly, mRNAs of the proneural transcription factors Foxp1, Foxp4, Hsf1, and Erf were among the targets that were translationally upregulated by SN3-L6. Either inhibition of translation or knockdown of these transcription factors blocked SN3-L6 activity. We finally confirmed that protein synthesis of a same set of transcription factors was upregulated in primary cortical NPCs. These findings together identify a new compound for translational activation and neuronal differentiation, and provide compelling evidence that reprogramming transcriptional regulation network at translational levels is a promising strategy for engineering NSPCs.

The sustainable development

International Nuclear Information System (INIS)

Robreau, Y.; Porcher, P.

2002-11-01

This document aims to define the sustainable development concept with a special attention for France and Israel position. The first part recalls the history of the sustainable development from the ''Man and Biosphere'' program of the UNESCO to Rio protocol. Then are described the principles of the sustainable development, the France plans and the France position at Johannesburg conference. The last part is devoted to the Israel position and a short presentation of the consequences of the greenhouse gases on the human health and the environment. (A.L.B.)

Sustainable Facilities Management

DEFF Research Database (Denmark)

Nielsen, Susanne Balslev; Elle, Morten; Hoffmann, Birgitte

2004-01-01

The Danish public housing sector has more than 20 years of experience with sustainable facilities management based on user involvement. The paper outlines this development in a historical perspective and gives an analysis of different approaches to sustainable facilities management. The focus...... is on the housing departments and strateies for the management of the use of resources. The research methods used are case studies based on interviews in addition to literature studies. The paper explores lessons to be learned about sustainable facilities management in general, and points to a need for new...

Sustainable Biofuels Development Center

Energy Technology Data Exchange (ETDEWEB)

Reardon, Kenneth F. [Colorado State Univ., Fort Collins, CO (United States)

2015-03-01

The mission of the Sustainable Bioenergy Development Center (SBDC) is to enhance the capability of America’s bioenergy industry to produce transportation fuels and chemical feedstocks on a large scale, with significant energy yields, at competitive cost, through sustainable production techniques. Research within the SBDC is organized in five areas: (1) Development of Sustainable Crops and Agricultural Strategies, (2) Improvement of Biomass Processing Technologies, (3) Biofuel Characterization and Engine Adaptation, (4) Production of Byproducts for Sustainable Biorefining, and (5) Sustainability Assessment, including evaluation of the ecosystem/climate change implication of center research and evaluation of the policy implications of widespread production and utilization of bioenergy. The overall goal of this project is to develop new sustainable bioenergy-related technologies. To achieve that goal, three specific activities were supported with DOE funds: bioenergy-related research initiation projects, bioenergy research and education via support of undergraduate and graduate students, and Research Support Activities (equipment purchases, travel to attend bioenergy conferences, and seminars). Numerous research findings in diverse fields related to bioenergy were produced from these activities and are summarized in this report.

36 CFR 219.20 - Ecological sustainability.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Ecological sustainability... Sustainability § 219.20 Ecological sustainability. To achieve ecological sustainability, the responsible official... diversity and species diversity are components of ecological sustainability. The planning process must...

Priority for sustainability. Final report

International Nuclear Information System (INIS)

2007-12-01

The Dutch Minister of Economic Affairs (EZ) has been asked to realize priority in connection to the grid for sustainable production capacity. Currently there are waiting lists for connection of new production capacity to the grid in some areas, due to a shortage in transport capacity. The Dutch connection policy (first come, first serve) may possibly lead to delays in connecting sustainable production capacity, which is not desirable in view of the incentivisation of sustainability. EZ and TenneT have asked Booz Allen to examine the options for giving priority to sustainability (wind and CHP). Priority in connection applies only to new sustainable production capacity, but priority in transport also applies to existing sustainable production capacity. [mk] [nl

Sustainable Public Bids

Directory of Open Access Journals (Sweden)

Gil César Costa de Paula

2016-06-01

Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

A New Agenda for Sustainability

DEFF Research Database (Denmark)

Aagaard Nielsen, Kurt

Two decades after the Brundtland Commission's Report "Our Common Future" adopted the concept of 'sustainable development', this book provides a renewal of the concept exploring the potential for new practices and fields for those involved in sustainability activity. The book addresses a number...... on sustainability. The material dealt with in the book offers a wide variety of perspectives on sustainability and reflects the importance of interdisciplinary and transdiciplinary work in the field. Suggesting targets for future analytical and political efforts in achieving global sustainability, this book offers...

Wrapping Our Brains around Sustainability

OpenAIRE

Mary Ann Curran

2009-01-01

As many of us begin to embrace the concept of sustainability, we realize that it is not simply something that we ‘do.’ Rather, sustainability is a destination that we aspire to reach with the selection of the sustainable pathways that we choose as we proceed along the journey. We are embarking on a new journey with the creation of Sustainability , an on-line, open access journal. As stated on the journal’s website, Sustainability is an international and cross-disciplinary scholarly journal of...

ORNL Annual Sustainability Report

Energy Technology Data Exchange (ETDEWEB)

Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2014-02-01

As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

Sustainability in coastal tourism development

DEFF Research Database (Denmark)

Andersen, Ida Marie Visbech; Blichfeldt, Bodil Stilling; Liburd, Janne J.

2018-01-01

explicitly requested nominations for sustainable tourism projects. A comparison between academic sustainability discourse and the approved projects suggests that tourism actors do not address sustainable tourism development as a holistic concept. Long-term perspectives are largely absent, whereas economic...... benefits are emphasized. Key findings also indicate weak political leadership in the envisaged transfer towards sustainable tourism development....

Investigation of Sustainable Housing Criteria

Directory of Open Access Journals (Sweden)

roshanfekr Somayeh

2016-01-01

Full Text Available Recently, much attention has been paid to sustainable development in cities. The quality of human life is directly related to environmental quality. Because many people live in cities as a place of social, economic and cultural relationships, certain issues such as environmental crises, energy, air and noise pollution and traffic jams are some of the factors that can alter the quality of human life. Therefore, in order to improve the quality of human life, attention to sustainable development (or sustainability in cities is proposed. Sustainable building has a comprehensive significance that begins with the conception of negative and positive impacts on the environment. Several descriptions of sustainable or green buildings have been created; however, they all pursue one goal, which is to create sustainable urban developments and protection of the environment. The quality of indoor environments, materials, and energy consumption, water usage, the impact of building construction processes and building maintenance are some of the factors that affect the environment and sustainability. Sustainable building is an attempt to relieve the minus impacts on the environment that occur during a building’s lifetime. This research investigates the important factors that have relevance to green buildings and introduces several criteria of sustainable housing.

Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

International Nuclear Information System (INIS)

Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

2010-01-01

Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke particles (DSP) induces upregulation of contractile endothelin type B (ET B ) receptors in rat cerebral arteries and if activation of mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) mediate the upregulation of contractile endothelin receptors in the cerebral arteries. Rat middle cerebral arteries were isolated and organ cultured in serum free medium for 24 h in the presence of DSP with or without specific inhibitors: MEK specific (U0126), p38 specific (SB202190), JNK specific (SP600125), NF-κB specific (BMS-345541) or (IMD-0354), transcription inhibitor (actinomycin D), or translation blocker (cycloheximide). Contractile responses to the ET B receptor agonist sarafotoxin 6c were investigated by a sensitive myograph. The expression of the ET B receptors were studied at mRNA and protein levels using quantitative real time PCR and immunohistochemistry, respectively. Results show that organ culture per se induced transcriptional upregulation of contractile ET B receptors in the cerebral vascular smooth muscle cells. This upregulation was further increased at the translational level by addition of DSP to the organ culture, but this increase was not seen by addition of nicotine or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET B receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK and JNK MAPK-mediated transcription and translation of new contractile ET B receptors. Thus, the MAPK-mediated upregulation of contractile ET B receptors in cerebral arteries might be a

Sustainable Procurement in Practice: Explaining the Degree of Sustainable Procurement from an Organisational Perspective

NARCIS (Netherlands)

J. Grandia (Jolien); S.M. Groeneveld (Sandra); B.S. Kuipers (Ben); A.J. Steijn (Bram)

2013-01-01

textabstractSustainable procurement is often used to reduce negative environmental impacts related to production and consumption. Several studies in the sustainable procurement literature have identified potential drivers of and barriers to sustainable procurement, which are often organisational in

Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

LENUS (Irish Health Repository)

Cronin, Patricia A

2010-05-21

Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

The indicators of the sustainable development

International Nuclear Information System (INIS)

1996-01-01

The 132 selected indicators of the sustainable development are described. They are grouped into: (1) The social indicators of the sustainable development; (2) The economic indicators of the sustainable development; (3) The environmental indicators of the sustainable development. (4) The institutional indicators of the sustainable development

PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.

Directory of Open Access Journals (Sweden)

Soledad A Camolotto

Full Text Available BACKGROUND: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression. Despite several transcription factors having been implicated as key regulators of PSG gene family expression; the role of protein acetylation has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here, we explored the role of acetylation on PSG gene expression in the human placental-derived JEG-3 cell line. Pharmacological inhibition of histone deacetylases (HDACs up-regulated PSG protein and mRNA expression levels, and augmented the amount of acetylated histone H3 associated with PSG 5'regulatory regions. Moreover, PSG5 promoter activation mediated by Sp1 and KLF6, via the core promoter element motif (CPE, -147/-140, was markedly enhanced in the presence of the HDAC inhibitor trichostatin A (TSA. This effect correlated with an increase in Sp1 acetylation and KLF6 nuclear localization as revealed by immunoprecipitation and subcellular fractionation assays. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetylase (HAT function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. CONCLUSIONS/SIGNIFICANCE: Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization.

The challenge of sustainability

International Nuclear Information System (INIS)

Orr, D.W.

1993-01-01

This paper discusses sustainability in a world that has changed rapidly. The author suggests that ecological assumptions embedded in communism and capitalism are badly flawed, but the flaws were not apparent when there were fewer than a billion people on earth living at low technology levels. Sustaining the earth's vital signs is a challenge to our perception of time, and the numbers - population, environmental damage, oil consumption, waste disposal - are too large to comprehend easily. There is a global debate about what sustainability means. In fact the challenge of sustainability is 6 different challenges: overcoming the tendency to deny inconvenient realities; establishing accurate indicators of human and ecological health; questions about the kinds of technology necessary to make the transition to sustainability; education; the need for an emotional bond between man and nature; rebuilding the existing democratic institutions. 16 refs

Catalysis and sustainable (green) chemistry

Energy Technology Data Exchange (ETDEWEB)

Centi, Gabriele; Perathoner, Siglinda [Dipartimento di Chimica Industriale ed Ingegneria dei Materiali, University of Messina, Salita Sperone 31, 98166 Messina (Italy)

2003-01-15

Catalysis is a key technology to achieve the objectives of sustainable (green) chemistry. After introducing the concepts of sustainable (green) chemistry and a brief assessment of new sustainable chemical technologies, the relationship between catalysis and sustainable (green) chemistry is discussed and illustrated via an analysis of some selected and relevant examples. Emphasis is also given to the concept of catalytic technologies for scaling-down chemical processes, in order to develop sustainable production processes which reduce the impact on the environment to an acceptable level that allows self-depuration processes of the living environment.

Diagnostic value of asymmetric striatal D2 receptor upregulation in Parkinson's disease: an [123I]IBZM and [123I]FP-CIT SPECT study

International Nuclear Information System (INIS)

Verstappen, C.C.P.; Bloem, B.R.; Haaxma, C.A.; Horstink, M.W.I.M.; Oyen, W.J.G.

2007-01-01

Striatal postsynaptic D 2 receptors in Parkinson's disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D 2 binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool. Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of ≤5 years and 26 age-matched controls. Striatal D 2 binding was assessed with [ 123 I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [ 123 I]FP-CIT SPECT. The mean striato-occipital ratio of [ 123 I]IBZM binding was significantly higher in PD patients (1.56 ±0.09) than in controls (1.53 ±0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 ±0.09 vs 1.55 ±0.10 ipsilaterally), suggesting D 2 receptor upregulation, and the reverse was seen using [ 123 I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation. Our study confirms asymmetric D 2 receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [ 123 I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D 2 receptors, assessed with [ 123 I]IBZM SPECT. (orig.)

Sustainable building organisation

NARCIS (Netherlands)

Schmid, P.

1998-01-01

Sustainable Development and Sustainable Building is mainly a question of (human) environmentally-conscious Organisation and Management Criteria are needed in order to capture the best practices in the field. Therefore we developed modells and methods, which help to choose the most adequate

Non-thermal plasma treatment diminishes fungal viability and up-regulates resistance genes in a plant host.

Science.gov (United States)

Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha

2014-01-01

Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance.

Fur and sustainability

DEFF Research Database (Denmark)

Skjold, Else; Ræbild, Ulla; Tanderup, Sisse

2016-01-01

interviews and observations at the premises of Kopenhagen Fur, as well as with stakeholders and collaborate partners in Denmark and in China. The definition of sustainability in the report must be seen as related to Design School Kolding's research umbrella of Sustainable Futures - a term chosen to unite...... practices around retail and communication (by Else Skjold, PhD in user studies and business management). On the basis of these four sub-projects, the report concludes the following: Currently, fur is placed very centrally in the moral debates around sustainability, as fur farming highligts environmental...... sustainability within the garment sector at large, and to define its own unique position for the future. With a departure in the the four sub-projects, the report lists a line of recommendations for how it would be possible to develop and revitalise traditional and current practices around fur design...

Transition to Sustainability: Science Support Through Characterizing and Quantifying Sustainability

Science.gov (United States)

Plag, Hans-Peter; Jules-Plag, Shelley

2013-04-01

Humanity's sustainability crisis caused by a growing, resource-demanding population on a finite, rapidly changing planet challenges us with large uncertainties. While some see the planet on the edge, it is more likely that humanity as a global species is on the edge. However, science, Earth observations, and socio-economic data do not provide clear indications of where this edge is, and how close we are to this edge. The instruments in the cockpit of a modern airplane provide more relevant and actionable information to the pilots than the "cockpit" of planet Earth provides to those involved in the governance of our planet. There is no manual for those responsible to keep us on a track within the "safe operational space" of humanity. What science and research is needed to make progress towards a future, where knowledge of sustainability and resilience allows for an evidence-based, adaptive policy and decision-making? Paradoxically, innovation over the recent decades have worsened the sustainablity crisis, but more innovation is imperative to bring us out of it. The comprehensive, conceptual framework for sustainability research that would provide an umbrella identifying the key challenges and a basis for this innovation seems to be missing. Defining sustainability as a characteristic of a process that can be maintained at a certain level indefinitely, we need to agree in a societal deliberation on a few aspects, including what processes we want to consider (the anthroposphere as embedded in the Earth system?), what time frames we want to aim at (not infinity, but very long time frames, e.g., 10,000 years?), and what spatial scales we need to look at (from local to global?). Most importantly, we need to acknowledge that humanity's sustainability is the result of intertwined social, economic, and environmental (s2e) processes that can not be separate. The research then has to clarify in the s2e context what are the attributes of sustainability, the relevant processes

Exergy sustainability.

Energy Technology Data Exchange (ETDEWEB)

Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

2006-05-01

Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

Genes up-regulated during red coloration in UV-B irradiated lettuce leaves.

Science.gov (United States)

Park, Jong-Sug; Choung, Myoung-Gun; Kim, Jung-Bong; Hahn, Bum-Soo; Kim, Jong-Bum; Bae, Shin-Chul; Roh, Kyung-Hee; Kim, Yong-Hwan; Cheon, Choong-Ill; Sung, Mi-Kyung; Cho, Kang-Jin

2007-04-01

Molecular analysis of gene expression differences between green and red lettuce leaves was performed using the SSH method. BlastX comparisons of subtractive expressed sequence tags (ESTs) indicated that 7.6% of clones encoded enzymes involved in secondary metabolism. Such clones had a particularly high abundance of flavonoid-metabolism proteins (6.5%). Following SSH, 566 clones were rescreened for differential gene expression using dot-blot hybridization. Of these, 53 were found to overexpressed during red coloration. The up-regulated expression of six genes was confirmed by Northern blot analyses. The expression of chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), and dihydroflavonol 4-reductase (DFR) genes showed a positive correlation with anthocyanin accumulation in UV-B-irradiated lettuce leaves; flavonoid 3',5'-hydroxylase (F3',5'H) and anthocyanidin synthase (ANS) were expressed continuously in both samples. These results indicated that the genes CHS, F3H, and DFR coincided with increases in anthocyanin accumulation during the red coloration of lettuce leaves. This study show a relationship between red coloration and the expression of up-regulated genes in lettuce. The subtractive cDNA library and EST database described in this study represent a valuable resource for further research for secondary metabolism in the vegetable crops.

Fostering Sustainable Travel Behavior: Role of Sustainability Labels and Goal-Directed Behavior Regarding Touristic Services

Directory of Open Access Journals (Sweden)

Elfriede Penz

2017-06-01

Full Text Available Individuals around the globe engage in sustainable consumption in their everyday life, e.g., when it comes to individual transportation. Although tourism behavior contributes to global carbon emissions to a considerable extent, consumers’ awareness of sustainability in the tourism industry is still underresearched. Placing eco-labels next to tourist offers on websites might direct consumer’s perception towards more sustainable offers. By employing eye-tracking techniques and surveys, this research aimed at linking information about sustainable tourist offers, perception of eco-labels and subsequent perception and preferences of tourism services. In Study 1, eight existing hotel offers with sustainability certification (four different labels were selected and their websites presented to 48 participants (four websites each, whose eye movements were tracked. After looking at each website, they rated the overall appearance of the website. Based on the results, in the second study, participants’ (n = 642 awareness of labels, their values and attitudes regarding sustainable behavior were found to influence their preference for certified tour operators. In addition, individuals’ ideas of their perfect holidays were captured to allow a better understanding of their motivation. This research proposes implementing appropriate sustainable labeling in the tourism industry to increase awareness about sustainability among travelers and subsequently increase sustainable travel behavior.

Sustained-Paced Finger Tapping: A Novel Approach to Measure Internal Sustained Attention

OpenAIRE

Marco A. Petilli; Marco A. Petilli; Daniela C. Trisolini; Roberta Daini; Roberta Daini; Roberta Daini

2018-01-01

Sustained attention is a fundamental prerequisite for all cognitive functions and its impairment is a common aftermath of both developmental and acquired neurological disorders. To date, all the sustained attention tasks rely heavily on selective attention to external stimuli. The interaction between selective and sustained attention represents a limit in the field of assessment and may mislead researchers or distort conclusions. The aim of the present perspective study was to propose a susta...

Profiling Sustainability Curriculum in AACSB Schools

Directory of Open Access Journals (Sweden)

Mukesh Srivastava

2014-04-01

Full Text Available This article describes the landscape of Sustainability Curriculum being used across the Association of Advance Collegiate Schools of Business (AACSB–accredited schools in the United States on the basis of a non-probabilistic sample (n = 119. Using hierarchical cluster analysis, four clusters were obtained based on sustainability-related courses in management, marketing, entrepreneurship, finance, accounting, information systems/information technology, strategy, globalization, communication, and miscellaneous. Cluster 1 had uniform dispersion on sustainability courses in all business courses except marketing. Clusters 2 and 4 were the largest ones with most sustainability courses in the management area, whereas, Cluster 3 had weak, but uniform, dispersion of sustainability courses in most business disciplines. Based on their characteristics and strength of dispersion among 10 business subject areas, these were labeled as Sustainability Prominent, Sustainability Moderate, Sustainability Meek, and Sustainability Quiescent.

Towards Life Cycle Sustainability Assessment

Directory of Open Access Journals (Sweden)

Marzia Traverso

2010-10-01

Full Text Available Sustainability is nowadays accepted by all stakeholders as a guiding principle for both public policy making and corporate strategies. However, the biggest challenge for most organizations remains in the real and substantial implementation of the sustainability concept. The core of the implementation challenge is the question, how sustainability performance can be measured, especially for products and processes. This paper explores the current status of Life Cycle Sustainability Assessment (LCSA for products and processes. For the environmental dimension well established tools like Life Cycle Assessment are available. For the economic and social dimension, there is still need for consistent and robust indicators and methods. In addition to measuring the individual sustainability dimensions, another challenge is a comprehensive, yet understandable presentation of the results. The “Life Cycle Sustainability Dashboard” and the “Life Cycle Sustainability Triangle” are presented as examples for communication tools for both experts and non expert stakeholders.

Sustainability in nursing: a concept analysis

Science.gov (United States)

Anåker, Anna; Elf, Marie

2014-01-01

Aim The aim of this study was to describe, explore and explain the concept of sustainability in nursing. Background Although researchers in nursing and medicine have emphasised the issue of sustainability and health, the concept of sustainability in nursing is undefined and poorly researched. A need exists for theoretical and empirical studies of sustainability in nursing. Design Concept analysis as developed by Walker and Avant. Method Data were derived from dictionaries, international healthcare organisations and literature searches in the CINAHL and MEDLINE databases. Inclusive years for the search ranged from 1990 to 2012. A total of fourteen articles were found that referred to sustainability in nursing. Results Sustainability in nursing involves six defining attributes: ecology, environment, future, globalism, holism and maintenance. Antecedents of sustainability require climate change, environmental impact and awareness, confidence in the future, responsibility and a willingness to change. Consequences of sustainability in nursing include education in the areas of ecology, environment and sustainable development as well as sustainability as a part of nursing academic programs and in the description of the academic subject of nursing. Sustainability should also be part of national and international healthcare organisations. The concept was clarified herein by giving it a definition. Conclusion Sustainability in nursing was explored and found to contribute to sustainable development, with the ultimate goal of maintaining an environment that does not harm current and future generations′ opportunities for good health. This concept analysis provides recommendations for the healthcare sector to incorporate sustainability and provides recommendations for future research. PMID:24602178

Comparison of Sustainable Soy : Initiatives in Brazil and Argentina. Do multiple standards enhance sustainability

NARCIS (Netherlands)

Valk, van der O.M.C.; Hospes, O.; Mheen-Sluijer, van der J.

2012-01-01

How sustainability schemes promote sustainability and compete amongst themselves is not static but in continuous movement. This is illustrated with the development history of sustainability schemes in soy. Their dynamics are defined by the importance of certified product for market access and by

Sustainable Academia: Translating the Vision of a Full Sustainable University into a Measurable Reality

Directory of Open Access Journals (Sweden)

Antonios Maragakis

2017-04-01

Full Text Available There is a growing public expectation that universities should start focusing on delivering sustainability. The topic of sustainability in higher education has gathered a significant amount of interest from students, academics, governments and international organizations. With a plethora of declarations, initiatives, marketing and assessments, there is a need to assess what the stakeholders want in order to make decisions regarding an institutions sustainability. Ultimately, students are the ones using these sustainability marketing materials to assist in their decision at which institution they will pursue their studies. The sheer volume of interpretations of the word sustainability with regards to higher education institution leaves ample room for potentially misguided initiatives or marketing. A universal system for assessing a higher educational institution’s sustainability has not been translated into a measurable reality. It is proposed that a universal system would help create a common understanding of sustainability within higher education institutions and would help in stakeholder understanding, institutional accountability and impactful application of sustainable initiatives. This research looked to answer if a holistic framework could be created that would aid stakeholders in reviewing a university’s level of sustainability. And, if so, if this vision of a fully sustainable university could be translated into a measurable reality. The research was approached in a structured way. Each chapter represents a published and peer-reviewed step towards addressing if a holistic framework could be created that would aid students in reviewing sustainability tools, assessments and marketing. The qualitative and quantitative conclusions from each chapter influenced the subsequent chapters, eventually leading to the creation and testing of two digital tools. The interpretations of these published chapters are found in the conclusion of this

SUSTAINABLE AND DESIGN BUILDING PROCESSES

Directory of Open Access Journals (Sweden)

Silvio F. R. MOTTA

2009-05-01

Full Text Available The article presents a historical revision of the sustainable development and the sustainable in the constructed environment. It describes the main concepts and practices for implantation of the sustainable in the civil construction. These concepts and practices are reviewed from the perspective of the dialectic method, the general theory of systems and the theories of creative processes. These concepts are also analyzed from the perspective of quality management. The article proposes a model based on the dialectic, in which sustainability is considered an open system and a search inventive. The implantation of the sustainable in projects, companies and design processes are considered as main strategy. A vertical insertion of the sustainable in the process is proposal. In this vertical insertion, the sustainable is presents in all the phases and activities of the process. The model is organized to promote the external creative solutions to the process, through the promotion of research centers. Tools of selection of possibilities and practical are suggested, considering the characteristic dialectics proposals. The article concludes that sustainable is a cultural change in the processes, practical and management current.

Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

OpenAIRE

Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.

2009-01-01

Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible ...

Urban Sustainability through Public Architecture

Directory of Open Access Journals (Sweden)

Soomi Kim

2018-04-01

Full Text Available As the sustainability of contemporary cities has gained emphasis, interest in architecture has increased, due to its social and public responsibility. Since sustainability is linked to public values, research on sustainable public spaces is an important way to secure sustainability in cities. Based on this, we analyzed the sustainability of European cities by examining the design methods of public architecture according to the region. The aim of the study is to derive architectural methodology corresponding to local characteristics, and to suggest issues to consider in public architecture design to promote urban sustainability based on this. First, regarding the environmental aspect, it can be observed that there is an effort to secure sustainability. Second, in terms of social sustainability, historical value remains as a trace of architectural place, so that it continues in people’s memory. In addition, public architecture provides public places where citizens can gather and enjoy programs, while the architectural methods showed differences influenced by cultural conditions. Third, in economic sustainability, it was shown that energy saving was achieved through cost reduction through recycling of materials, facilities, or environmental factors. In conclusion, the issues to be considered in public architectural design are the voiding of urban space through architectural devices in the construction method. In other words, the intention is to form “ground” that attempts to be part of the city, and thereby create better places. Since skin and material have a deep relationship with the environment, they should have the durability and an outer skin that are suitable for the regional environment. Finally, sustainability is to be utilized through the influx of programs that meet local and environmental characteristics. Design research into public architecture that is oriented towards urban sustainability will be a task to be carried out by the

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Bian, Yong, E-mail: drbiany@126.com [Department of Science and Technology, Nanjing University of Chinese Medicine, 210023 (China); Yu, Yun [College of Pharmacy, Nanjing University of Chinese Medicine, 210023 (China); Wang, Shanshan; Li, Lin [Department of Science and Technology, Nanjing University of Chinese Medicine, 210023 (China)

2015-08-07

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

International Nuclear Information System (INIS)

Bian, Yong; Yu, Yun; Wang, Shanshan; Li, Lin

2015-01-01

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression

Sustainability dilemmas in emerging economies

Directory of Open Access Journals (Sweden)

Rama K. Jayanti

2014-06-01

Full Text Available Increasing evidence of climate change is forcing businesses to play an active role in reducing sustainability burdens and preserving resources for future generations. Extant research on sustainability has an exclusive focus on developed countries with stringent environmental regulations and activist scrutiny. Emerging markets present interesting dilemmas since rapid mass urbanisation aimed at raising standards of living poses concomitant threats to environmental health. This round table aimed to showcase best practices in sustainability within the Indian business context. Insights from the discussion regarding sustainability dilemmas provide a fertile ground for bench marking global sustainability best practices.

Sustainability in Fashion Business Operations

Directory of Open Access Journals (Sweden)

Tsan-Ming Choi

2015-11-01

Full Text Available Under the global trend of sustainability, many companies selling fashion products have to reshape their operational strategies. Over the past few years, we have witnessed many fashion companies going green by re-engineering their business processes and establishing their formal sustainability programs. Many important topics, such as closed-loop supply chain management, corporate social responsibility, and economic sustainability, are all related to sustainable fashion business operations management. This paper provides a brief review of these critical topics, introduces the special issue, and proposes future research areas to achieve sustainable operations management in the fashion business.

Y-12 Site Sustainability Plan

Energy Technology Data Exchange (ETDEWEB)

Sherry, T D; Kohlhorst, D P; Little, S K

2011-12-01

The accomplishments to date and the long-range planning of the Y-12 Energy Management and Sustainability and Stewardship programs support the DOE and the National Nuclear Security Administration (NNSA) vision for a commitment to energy efficiency and sustainability and to achievement of the Guiding Principles. Specifically, the Y-12 vision is to support the Environment, Safety and Health Policy and the DOE Strategic Sustainability Performance Plan (SSPP) while promoting overall sustainability and reduction of greenhouse gas (GHG) emissions. Table ES.2 gives a comprehensive overview of Y-12's performance status and planned actions. B&W Y-12's Energy Management mission is to incorporate renewable energy and energy efficient technologies site-wide and to position Y-12 to meet NNSA energy requirement needs through 2025 and beyond. During FY 2011, the site formed a sustainability team (Fig. ES.1). The sustainability team provides a coordinated approach to meeting the various sustainability requirements and serves as a forum for increased communication and consistent implementation of sustainability activities at Y-12. The sustainability team serves as an information exchange mechanism to promote general awareness of sustainability information, while providing a system to document progress and to identify resources. These resources are necessary to implement activities that support the overall goals of sustainability, including reducing the use of resources and conserving energy. Additionally, the team's objectives include: (1) Foster a Y-12-wide philosophy to conserve resources; (2) Reduce the impacts of production operations in a cost-effective manner; (3) Increase materials recycling; (4) Use a minimum amount of energy and fuel; (5) Create a minimum of waste and pollution in achieving Y-12-strategic objectives; (6) Develop and implement techniques, technologies, process modifications, and programs that support sustainable acquisition; (7) Minimize the

The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

Energy Technology Data Exchange (ETDEWEB)

Cao, Lei [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden); Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Ping, Na-Na; Cao, Yong-Xiao [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Li, Wei, E-mail: 13572512207@163.com [Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Cai, Yan [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Warfvinge, Karin; Edvinsson, Lars [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden)

2016-08-01

Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET{sub A} receptor mRNA and protein levels as well as contractile responses mediated by ET{sub A} receptors. The immunoreactivity of increased ET{sub A} receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET{sub B} receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET{sub A} receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET{sub A} receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the

The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

International Nuclear Information System (INIS)

Cao, Lei; Ping, Na-Na; Cao, Yong-Xiao; Li, Wei; Cai, Yan; Warfvinge, Karin; Edvinsson, Lars

2016-01-01

Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET A receptor mRNA and protein levels as well as contractile responses mediated by ET A receptors. The immunoreactivity of increased ET A receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET B receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET A receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET A receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the treatment of SHS

Sustainable economic structures

NARCIS (Netherlands)

Dellink, R.B.; Bennis, M.; Verbruggen, H.

1999-01-01

The paper introduces four scenarios for sustainable economic structures in the Netherlands for 2030. The aim of this paper is to provide possible answers to what a sustainable future might look like in terms of alternative economic structures. To this end, an empirical economy-ecology model is

Work activities within sustainable development

Directory of Open Access Journals (Sweden)

Francisco Duarte

2015-06-01

Full Text Available This paper presents the main results of a Franco-Brazilian Research project entitled "Work, Innovation and Development". The aim is to conceptually consider work activity within sustainable development, and to contribute methodologically towards developing strategies for designing sustainable work systems. After a brief description of the factors and the dimensions that have contributed to the creation of ideas on sustainable development, we will put forward two main approaches for understanding work activity within the context of sustainability, these being: the durability of work activity and the development of work activities for sustainable development. Both approaches are presented and examples are given. This is followed by a discussion of the design of sustainable work systems that focuses particularly on the political and technical dimensions of project management.

Towards a Sustainable Architecture

OpenAIRE

Patuel Chust, Pascual

2014-01-01

The growing awareness of the importance of ecology in the last decades has led many architects to rethink their construction proposals to make them more respectful of the environment and sustainability. The present article analyzes the legislation, conferences and international declarations (Earth Summit, Declaration of Interdependence for a Sustainable Future, Introduction to Sustainable Design) that have advocated the practice of a more ecological architecture. Also examined ...

Sustainability in nursing: a concept analysis.

Science.gov (United States)

Anåker, Anna; Elf, Marie

2014-06-01

The aim of this study was to describe, explore and explain the concept of sustainability in nursing. Although researchers in nursing and medicine have emphasised the issue of sustainability and health, the concept of sustainability in nursing is undefined and poorly researched. A need exists for theoretical and empirical studies of sustainability in nursing. Concept analysis as developed by Walker and Avant. Data were derived from dictionaries, international healthcare organisations and literature searches in the CINAHL and MEDLINE databases. Inclusive years for the search ranged from 1990 to 2012. A total of fourteen articles were found that referred to sustainability in nursing. Sustainability in nursing involves six defining attributes: ecology, environment, future, globalism, holism and maintenance. Antecedents of sustainability require climate change, environmental impact and awareness, confidence in the future, responsibility and a willingness to change. Consequences of sustainability in nursing include education in the areas of ecology, environment and sustainable development as well as sustainability as a part of nursing academic programs and in the description of the academic subject of nursing. Sustainability should also be part of national and international healthcare organisations. The concept was clarified herein by giving it a definition. Sustainability in nursing was explored and found to contribute to sustainable development, with the ultimate goal of maintaining an environment that does not harm current and future generations' opportunities for good health. This concept analysis provides recommendations for the healthcare sector to incorporate sustainability and provides recommendations for future research. © 2014 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.

The Implementation of Corporate Sustainability in the European Automotive Industry: An Analysis of Sustainability Reports

Directory of Open Access Journals (Sweden)

Martina Sukitsch

2015-08-01

Full Text Available The acceptance of corporate sustainability implementation and sustainability reporting has continued to grow steadily in recent years. This is particularly true for companies in the automotive industry. Increasing regulatory demands, for example, with respect to CO2 emissions, are one clear reason for this. In this paper the sustainability reports of 14 manufacturers in the European automotive industry are analyzed with respect to issues of corporate sustainability implementation. This entails content analysis of sustainability reports from 2012, and of their earliest available equivalents. The analysis of corporate sustainability implementation in the selected companies is provided with the purpose to help understand how manufacturers in the European automotive industry implement corporate sustainability. Results confirm the importance of specific policy instruments in implementation, such as the use of environmental management systems and standards, and of related changes in organizational structures. The latter include suitable adaptation of corporate strategy, philosophy, objectives, measures, and activities, as well as the need to integrate stakeholders in the adjustment process. The analysis shows that while companies are well-aware of the significance of sustainability for their industry, some tend to be leaders, and others laggards, as far as implementation is concerned.

Towards Science for Democratic Sustainable Development

DEFF Research Database (Denmark)

Mortensen, Jonas Egmose

residents, sustainability resear- chers and practitioners in deliberating on how future research can meet societal challenges of urban sustainability. Based on the research project Citizen Science for Sustainability (SuScit) I analyse how orientations towards sustainability can be understood and challenged...... of urban everyday life, confronting academic concepts of sustainability. This process not at least calls for reflexivity among researchers facing the challenge how science can further sustainability through community engagement. To conceptualise this dynamic I propose the concept of creation and doubling...

Developing a comprehensive definition of sustainability.

Science.gov (United States)

Moore, Julia E; Mascarenhas, Alekhya; Bain, Julie; Straus, Sharon E

2017-09-02

Understanding sustainability is one of the significant implementation science challenges. One of the big challenges in researching sustainability is the lack of consistent definitions in the literature. Most implementation studies do not present a definition of sustainability, even when assessing sustainability. The aim of the current study was to systematically develop a comprehensive definition of sustainability based on definitions already used in the literature. We searched for knowledge syntheses of sustainability and abstracted sustainability definitions from the articles identified through any relevant systematic and scoping reviews. The constructs in the abstracted sustainability definitions were mapped to an existing definition. The comprehensive definition of sustainability was revised to include emerging constructs. We identified four knowledge syntheses of sustainability, which identified 209 original articles. Of the 209 articles, 24 (11.5%) included a definition of sustainability. These definitions were mapped to three constructs from an existing definition, and nine new constructs emerged. We reviewed all constructs and created a revised definition: (1) after a defined period of time, (2) a program, clinical intervention, and/or implementation strategies continue to be delivered and/or (3) individual behavior change (i.e., clinician, patient) is maintained; (4) the program and individual behavior change may evolve or adapt while (5) continuing to produce benefits for individuals/systems. All 24 definitions were remapped to the comprehensive definition (percent agreement among three coders was 94%). Of the 24 definitions, 17 described the continued delivery of a program (70.8%), 17 mentioned continued outcomes (70.8%), 13 mentioned time (54.2%), 8 addressed the individual maintenance of a behavior change (33.3%), and 6 described the evolution or adaptation (25.0%). We drew from over 200 studies to identify 24 existing definitions of sustainability

Gemfibrozil and Fenofibrate, Food and Drug Administration-approved Lipid-lowering Drugs, Up-regulate Tripeptidyl-peptidase 1 in Brain Cells via Peroxisome Proliferator-activated Receptor α

Science.gov (United States)

Ghosh, Arunava; Corbett, Grant T.; Gonzalez, Frank J.; Pahan, Kalipada

2012-01-01

The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene is Cln2, encoding tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there is no established treatment for this fatal disease. This study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic activity of TPP1 in primary mouse neurons and astrocytes as well as human astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to activate peroxisome proliferator-activated receptor-α (PPARα), the role of PPARα in gemfibrozil- and fenofibrate-mediated up-regulation of TPP1 was investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and enzymatic activity both in vitro and in vivo in wild type (WT) and PPARβ−/−, but not PPARα−/−, mice. In an attempt to delineate the mechanism of TPP1 up-regulation, it was found that the effects of the fibrate drugs were abrogated in the absence of retinoid X receptor-α (RXRα), a molecule known to form a heterodimer with PPARα. Accordingly, all-trans-retinoic acid, alone or together with gemfibrozil, up-regulated TPP1. Co-immunoprecipitation and ChIP studies revealed the formation of a PPARα/RXRα heterodimer and binding of the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs via PPARα/RXRα pathway. PMID:22989886

The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism.

Science.gov (United States)

Liu, Tianhui; Wang, Ping; Cong, Min; Xu, Youqing; Jia, Jidong; You, Hong

2013-06-05

DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

Undergraduates in a Sustainability Semester: Models of Social Change for Sustainability

Science.gov (United States)

Miller, Hannah K.

2016-01-01

Interdisciplinary sustainability programs are emerging globally, but little is known about the learning in these educational contexts. This qualitative case study examined undergraduates' experience in a Sustainability Semester, using the agency/structure dialectic as a theoretical lens. Before the semester, students' models of change for…

Design for Sustainability : Current Trends in Sustainable Product Design and Development

NARCIS (Netherlands)

Clark, G.; Kosoris, J.; Nguyen Hong, L.; Crul, M.

2009-01-01

The Design for Sustainability (D4S) concept outlines methodologies for making sustainable improvements (social, economic and environmental) to products by applying elements of life cycle thinking. D4S builds on the work of ecodesign to include economic and social concerns, and its methodology

Upregulation of Nicotinic Acetylcholine Receptor alph4+beta2 through a Ligand-Independent PI3Kbeta Mechanism That Is Enhanced by TNFalpha and the Jak2/p38Mapk Pathways.

Science.gov (United States)

Rogers, Scott W; Gahring, Lorise C

2015-01-01

High affinity nicotine-binding sites in the mammalian brain are neuronal nicotinic acetylcholine receptors (nAChR) assembled from at least alpha4 and beta2 subunits into pentameric ion channels. When exposed to ligands such as nicotine, these receptors respond by undergoing upregulation, a correlate of nicotine addiction. Upregulation can be measured using HEK293 (293) cells that stably express alpha4 and beta2 subunits using quantification of [3H]epibatidine ([3H]Eb) binding to measure mature receptors. Treatment of these cells with choline also produces upregulation through a hemicholinium3 (HC3)-sensitive (choline kinase) and an HC3-insensitive pathway which are both independent of the mechanism used by nicotine for upregulation. In both cases, upregulation is significantly enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) which signals through its receptor Tnfr1 to activate p38Mapk. Here we report that the inhibition of class1 phosphoinositide 3-kinases isoform PI3Kbeta using the selective antagonist PI828 is alone sufficient to produce upregulation and enhance both nicotine and choline HC3-sensitive mediated upregulation. Further, these processes are impacted upon by an AG-490 sensitive Jak2-associated pathway. Both PI3Kbeta (negative) and Jak2 (positive) modulation of upregulation converge through p38Mapk and both overlap with TNFalpha enhancement of this process. Upregulation through the PI3Kbeta pathway did not require Akt. Collectively these findings support upregulation of endogenous alpha4beta2 as a balance among cellular signaling networks that are highly responsive to multiple environmental, inflammatory and metabolic agents. The findings also suggest how illness and metabolic stress could alter the expression of this important nicotinic receptor and novel avenues to intercede in modifying its expression.

Factors Affecting Entrepreneurship and Business Sustainability

Directory of Open Access Journals (Sweden)

Ana Tur-Porcar

2018-02-01

Full Text Available Sustainability is becoming increasingly important for society, and the creation of business ventures is one area where sustainability is critical. We examined the factors affecting actions that are designed to foster business sustainability. These factors are related to the environment, behavior, human relations, and business activity. Based on questionnaire responses from experts, the Analytic Hierarchy Process (AHP method was used to rank sustainable business criteria according to their importance for entrepreneurs starting sustainable businesses. The results indicate that the most important drivers of sustainable entrepreneurship are behavioral factors and business factors. Ethical principles and values, together with competitive intelligence, are crucial for undertaking actions that lead to sustainability.

Sustainability in Canadian Post-Secondary Institutions: The Interrelationships among Sustainability Initiatives and Geographic and Institutional Characteristics

Science.gov (United States)

Beveridge, Dan; McKenzie, Marcia; Vaughter, Philip; Wright, Tarah

2015-01-01

Purpose: This paper aims to report on a census of high-level sustainability initiatives at all accredited post-secondary institutions in Canada by documenting the institutions that have undertaken sustainability assessments, have signed one or more sustainability declarations, have sustainability offices or officers or have sustainability…

Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

Directory of Open Access Journals (Sweden)

Sachiko Hirai

Full Text Available Up-regulated sirtuin 1 (SIRT1, an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53. Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5. In the KatoIII cell line (TP53-null, DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.

Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth.

Science.gov (United States)

Chaillou, Thomas; Jackson, Janna R; England, Jonathan H; Kirby, Tyler J; Richards-White, Jena; Esser, Karyn A; Dupont-Versteegden, Esther E; McCarthy, John J

2015-01-01

The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. Copyright © 2015 the American Physiological Society.

Seeking Sustainability

OpenAIRE

Clive L. Spash

2014-01-01

What does sustainability research do to help the environment? One might well wonder when observing the annual conference season with various academics and professors in sustainability science, ecological economics or environmental ethics driving to the airport to fly off to international meetings to discuss how bad things are getting, what should been done about it, and how time is running out for action. In fact, singling out a few academic groups is highly unfair because the link between pr...

The role of sustainable HORECA for sustainable lifestyles - identification of challenges and future work

DEFF Research Database (Denmark)

Strassner, Carola; Bügel, Susanne Gjedsted; Hertwig, Jostein

2016-01-01

Internationally there is increasing interest in short food supply chains and local and organic food as part of a wider concern with sustainability. This is strongly evident in both commercially oriented food service, where it is often associated with sustainable tourism endeavours, and in institu......Internationally there is increasing interest in short food supply chains and local and organic food as part of a wider concern with sustainability. This is strongly evident in both commercially oriented food service, where it is often associated with sustainable tourism endeavours...

Agroecology and Sustainable Agriculture

Directory of Open Access Journals (Sweden)

Fabio Caporali

Full Text Available In the framework of the 16th National Meeting of the Italian Ecological Society (“Global Change, Ecological Diversity and Sustainability”, University of Tuscia, Viterbo, 19-22 September 2006, a symposium was devoted to “Agroecology and Sustainable Development”. A major goal of this symposium was to contribute to keeping the dialogue among the experts of the various disciplines alive. Sustainability of agriculture is a challenge for society world wide. Universities and society as a whole have a responsibility in re-examining current perception of nature, of the world and of human society in the light of natural resources depletion, increasing pollution and social inequalities. The urgency to address sustainability issues is increasingly being reflected in the manner in which institutions of higher education around the world are giving priority to the teaching, research and practice of sustainability. The University of Tuscia is involved in international initiatives concerning teaching and research in Agroecology and Sustainable Agriculture.

APPROACHES FOR SUSTAINABLE MANUFACTURING

Institute of Scientific and Technical Information of China (English)

G(U)NTHER Seliger; SEBASTIAN Kernbaum; MARCO Zettl

2007-01-01

Sustainable development is a holistic approach harmonizing ecological, economical and socio-political needs with respect to the superior objective of enhancing human living standards. Thereby the availability of natural resources and the conservation of the ecosystems have to be considered that future generations have the possibility to meet their own needs. A long-term economical development demands the transition from a source-sink economy to a cycle economy as a result of limited resources, limited environmental capacities to absorb waste and emissions as well as increasing needs of a growing population. A reference model for sustainability in manufacturing is presented and used to illustrate sustainable approaches with respect to management, technology, process and product. Adaptation of products and components is a vital element for supporting efficient reuse of products and components. Consequently adaptation contributes to the ambitious goals of sustainability. Technological enablers for adaptation as modularity, information and communication technology are exemplarily introduced. Moreover, approaches for disseminating knowledge in sustainability are given.

Sustainable nuclear energy dilemma

Directory of Open Access Journals (Sweden)

Afgan Naim H.

2013-01-01

Full Text Available Sustainable energy development implies the need for the emerging potential energy sources which are not producing adverse effect to the environment. In this respect nuclear energy has gained the complimentary favor to be considered as the potential energy source without degradation of the environment. The sustainability evaluation of the nuclear energy systems has required the special attention to the criteria for the assessment of nuclear energy system before we can make firm justification of the sustainability of nuclear energy systems. In order to demonstrate the sustainability assessment of nuclear energy system this exercise has been devoted to the potential options of nuclear energy development, namely: short term option, medium term option, long term option and classical thermal system option. Criteria with following indicators are introduced in this analysis: nuclear indicator, economic indicator, environment indicator, social indicator... The Sustainability Index is used as the merit for the priority assessment among options under consideration.

Sustainability and Organizational Change

Directory of Open Access Journals (Sweden)

Catălina Sitnikov

2012-06-01

Full Text Available The relevant and, above all, remarkable feature of sustainability is due to its "duality": on the one hand, it is an indispensable element within the companies even if, on the other hand, it increases the costs of many activities and processes. Facing the challenge of sustainability will determine and create, in the coming years, emerging organizational forms. If ten years ago, many managers clearly expressed their doubts regarding the financial feasibility of sustainability, today, they admit the importance of sustainability for the competitive advantage of the companies they manage. Currently, companies have great opportunities to support build a sustainable global economy, becoming one of the solutions to the most pressing societal challenges. Whether it is about reducing pollution, global warming, reducing use of water resources and other limited resources or ensuring a better work environment for employees throughout the supply chain, there are many things that companies can and should do.

The relationship between settlement population size and sustainable development measured by two sustainability metrics

International Nuclear Information System (INIS)

O'Regan, Bernadette; Morrissey, John; Foley, Walter; Moles, Richard

2009-01-01

This paper reports on a study of the relative sustainability of 79 Irish villages, towns and a small city (collectively called 'settlements') classified by population size. Quantitative data on more than 300 economic, social and environmental attributes of each settlement were assembled into a database. Two aggregated metrics were selected to model the relative sustainability of settlements: Ecological Footprint (EF) and Sustainable Development Index (SDI). Subsequently these were aggregated to create a single Combined Sustainable Development Index. Creation of this database meant that metric calculations did not rely on proxies, and were therefore considered to be robust. Methods employed provided values for indicators at various stages of the aggregation process. This allowed both the first reported empirical analysis of the relationship between settlement sustainability and population size, and the elucidation of information provided at different stages of aggregation. At the highest level of aggregation, settlement sustainability increased with population size, but important differences amongst individual settlements were masked by aggregation. EF and SDI metrics ranked settlements in differing orders of relative sustainability. Aggregation of indicators to provide Ecological Footprint values was found to be especially problematic, and this metric was inadequately sensitive to distinguish amongst the relative sustainability achieved by all settlements. Many authors have argued that, for policy makers to be able to inform planning decisions using sustainability indicators, it is necessary that they adopt a toolkit of aggregated indicators. Here it is argued that to interpret correctly each aggregated metric value, policy makers also require a hierarchy of disaggregated component indicator values, each explained fully. Possible implications for urban planning are briefly reviewed

ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

International Nuclear Information System (INIS)

Zhou, Yan; Ming, Jia; Xu, Yan; Zhang, Yi; Jiang, Jun

2015-01-01

Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis

Motivations Behind Sustainable Purchasing

OpenAIRE

Vörösmarty, Gyöngyi; Dobos, Imre; Tátrai, Tünde

2011-01-01

Sustainability issues in purchasing are receiving greater attention. Literature is rapidly growing, with several research programs being initiated to investigate the topic. This study presents the results of a research project which aims to reveal and structure the motivating forces leading companies to make efforts in sustainability purchasing and the means used to attain achievements in some fields of sustainability. Results presented in the literature are scattered in terms of ...

Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells.

Science.gov (United States)

Min, Kyoung-Jin; Nam, Ju-Ock; Kwon, Taeg Kyu

2017-08-02

Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

Sustainable DTU, Electronics and It

DEFF Research Database (Denmark)

Schultz, Ole; Molin, Jesper; Hundebøll, Peder M.

2014-01-01

and suggest what should be done at the Campus to make it green and as the last part of it the prototype and suggest in detail what could be done. Over time there have been participating students from another elective course, Sustainable Electronics and IT as well students from Process and Innovation, Export...... Engineering and Civil Engineering students. The courses teach students that sustainability is a cross disciplinary topic – where engineering’s from different education has to cooperate for getting a proper solution. Electronic and IT Diplom engineering students are motivated learning about sustainability...... within their field when sustainability and environmental impact is seen in a context. That is done in an elective course: Sustainable Electronics and IT (SUSIE). We have integrated sustainability in the context of embedded wireless systems for building monitoring and control using the Internet of Things...

Up-regulation of ALG-2 in hepatomas and lung cancer tissue

DEFF Research Database (Denmark)

la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

2003-01-01

, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

Entrepreneurial action, sustainability and bricolage

DEFF Research Database (Denmark)

Korsgaard, Steffen T.

This paper explores the relation between entrepreneurship and sustainability. It is explored whether bricolage, a specific form of entrepreneurial action, is particularly conducive to the creation of sustainable solutions. This question is investigated through a case study of an entrepreneur who...... has a long history of sustainable entrepreneurship in which bricolage plays a central role. The study identifies six distinct forms of bricolage practised by the entrepreneur. Furthermore, it is found that, while there is no direct link between bricolage and sustainability, the two concepts have...... a potentially synergetic relationship between them so that bricolage skills may enhance a sustainable mindset, and vice versa....

Sustainable development - an entrepreneur's view

International Nuclear Information System (INIS)

Fahrni, F.

1995-01-01

The following topics are dealt with in this paper: prizing the environment, inducing change, getting the right mix, energy and market place, financing sustainable development, trade and sustainable development, managing corporate change, the Sulzer strategy for sustainable development. (author)

Analyse that! : understanding sustainable design

NARCIS (Netherlands)

Brand, van den G.J.W.; Wit, de M.H.

2004-01-01

This paper describes a method for the analysis of sustainable building projects. Sustainable technology measures can easily be misinterpreted, consequently leading to unsustainable building solutions. Our research and educations aims at discovering new approaches for sustainable design. For building

Strategic Leadership of Corporate Sustainability

DEFF Research Database (Denmark)

Strand, Robert

2014-01-01

Strategic leadership and corporate sustainability have recently come together in conspicuously explicit fashion through the emergence of top management team (TMT) positions with dedicated corporate sustainability responsibilities. These TMT positions, commonly referred to as 'Chief Sustainability......? What effects do corporate sustainability TMT positions have at their organizations? We consider these questions through strategic leadership and neoinstitutional theoretical frameworks. Through the latter, we also engage with Weberian considerations of bureaucracy. We find that the reasons why...

Campus Sustainability Governance in Canada: A Content Analysis of Post-Secondary Institutions' Sustainability Policies

Science.gov (United States)

Vaughter, Philip; McKenzie, Marcia; Lidstone, Lauri; Wright, Tarah

2016-01-01

Purpose: This paper aims to provide an overview of a content analysis of sustainability policies from Canadian post-secondary education institutions. The paper reports findings on the orientations to sustainability evident in the policies; references to other policies within the documents; and other key themes on how sustainability is engaged in…

Corporate Sustainability Management and Environmental Ethics

DEFF Research Database (Denmark)

Schuler, Douglas; Rasche, Andreas; Etzion, Dror

2017-01-01

This article reviews four key orientations in environmental ethics that range from an instrumental understanding of sustainability to one that acknowledges the intrinsic value of sustainable behavior (i.e., sustainable resource use, conservation and preservation, rights-based perspectives, and deep...... ecology). It then shows that the current scholarly discourse around corporate sustainability management—as reflected in environment management (EM), corporate social responsibility (CSR), and corporate political activity (CPA)—mostly favors an instrumental perspective on sustainability. Sustainable...... business practices are viewed as anthropocentric and are conceptualized as a means to achieve competitive advantage. Based on these observations, we speculate about what corporate sustainability management might look like if it applied ethical orientations that emphasize the intrinsic value of nature...

Engineering and Sustainability: Attitudes and Actions

Directory of Open Access Journals (Sweden)

Marc A. Rosen

2013-01-01

Full Text Available The results of an extensive survey of engineers and engineering students suggest there is a strong focus on the implementation of sustainability concepts, actions and measures in engineering. The main sustainable technology priorities are using less energy and natural resources, reducing emissions and material wastes, and utilizing renewable, recyclable and recycled materials. Sustainable engineering within organizations is mainly driven by regulatory requirements, rising energy costs and client demand, but challenges to sustainable engineering like economics need to be addressed to increase the incorporation of sustainability in engineering. Nonetheless, about two-thirds of practicing engineers have worked on sustainable products and processes, and over half of engineering students are involved with sustainable design in their studies.

Sustainability in the food sector

DEFF Research Database (Denmark)

Grunert, Klaus G

2011-01-01

Consumers have, through their food choices, a major role in bringing about more sustainable food production. However, this presupposes that differences in sustainability are communicated to consumers. Even if food products are eco-labelled and consumers are motivated to support sustainability...

Sustainability Science Needs Sustainable Data!

Science.gov (United States)

Downs, R. R.; Chen, R. S.

2013-12-01

Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

SUSTAINABLE DEVELOPMENT, A MULTIDIMENSIONAL CONCEPT

Directory of Open Access Journals (Sweden)

TEODORESCU ANA MARIA

2015-06-01

Full Text Available Sustainable development imposed itself as a corollary of economic term "development". Sustainable development is meant to be the summation of economic, environmental and social considerations for the present and especially for the future. The concept of sustainable development plays an important role in european and global meetings since 1972, the year it has been set for the first time. Strategies necessary to achieve the objectives of sustainable development have been developed, indicators meant to indicate the result of the implementation of policies have been created, national plans were oriented towards achieving the proposed targets. I wanted to highlight the multidimensional character of the concept of sustainable development. Thus, using specialized national and international literature, I have revealed different approaches of one pillar to the detriment of another pillar depending on the specific field. In the different concepts of sustainable development, the consensus is undoubtedly agreed on its components: economic, social, environmental. Based on this fact, the concept of sustainability has different connotations depending on the specific content of each discipline: biology, economics, sociology, environmental ethics. The multidimensional valence of sustainable development consists of three pillars ability to act together for the benefit of present and future generations. Being a multidimensional concept, importance attached to a pillar over another is directed according to the particularities of each field: in economy profit prevails, in ecology care of natural resources is the most important, the social aims improving human living conditions. The challenge of sustainable development is to combine all the economic, environmental and social benefits and the present generation to come. Ecological approach is reflected in acceptance of limited natural resources by preserving natural capital. In terms of the importance of

Teaching environmental sustainability in higher education

NARCIS (Netherlands)

Itard, L.C.M.; Van den Bogaard, M.E.D.; Hasselaar, E.

2010-01-01

The challenges of sustainable engineering and design are complex and so are the challenges of teaching sustainability to higher education students. This paper deals with teaching environmental sustainability, with a specific focus on the sustainability of buildings. The paper addresses specifically

Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

International Nuclear Information System (INIS)

Eftang, Lars L; Esbensen, Ying; Tannæs, Tone M; Blom, Gustav P; Bukholm, Ida RK; Bukholm, Geir

2013-01-01

The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance.

Science.gov (United States)

Tsai, Pei-Yun; Zhang, Bingkun; He, Wei-Qi; Zha, Juan-Min; Odenwald, Matthew A; Singh, Gurminder; Tamura, Atsushi; Shen, Le; Sailer, Anne; Yeruva, Sunil; Kuo, Wei-Ting; Fu, Yang-Xin; Tsukita, Sachiko; Turner, Jerrold R

2017-06-14

Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na + channel formed by claudin-2. Relative to wild-type, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2-deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance. Copyright © 2017 Elsevier Inc. All rights reserved.

Principles and practices of sustainable water management

Institute of Scientific and Technical Information of China (English)

Bixia Xu

2010-01-01

Literature related to sustainable water management is reviewed to illustrate the relationship among water management, sustainability (sustainable development), and sustainable water management. This review begins with the explanation on the definition of sustainable water management, followed by a discussion of sustainable water management principles and practices.

Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome.

Science.gov (United States)

Shaw, Jillian L; Zhang, Shixing; Chang, Karen T

2015-08-12

Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results

Sustainable spatial development in higher education

Directory of Open Access Journals (Sweden)

Maja Terlević

2015-06-01

Full Text Available Sustainable development is not only a great challenge for society as a whole, but also for higher education institutions, which have been rapidly including sustainable development in their educational process in the last two decades. Directly or indirectly, education for sustainable spatial development includes all aspects of sustainable development: environmental, economic, social and cultural. Space is a junction of various interests, which requires coordinating the entire process of spatial planning, taking into account the goal of sustainable spatial development. The existing values of space are insufficient for the rapid implementation of a sustainable spatial development paradigm. Suitable education is needed by both individuals and spatial planning professionals and at all levels of education. It is therefore necessary to transform some of the academic programs in the higher education curriculum by integrating teaching content and methods that include long-term knowledge and holistic thinking, taking into account the importance of interdisciplinary integration. This article reviews literature in sustainable development in higher education from 2002 to 2013. Topics discussed include students’ and teachers’ conceptions of sustainable development, the presence of sustainable development and sustainable spatial development in higher education and the reasons for the slow introduction of this material into the curriculum. Based on a literature analysis, the last section identifies important drivers that can contribute to a more rapid integration of a sustainable spatial development paradigm into higher education.

Sustaining Urban Forests

Science.gov (United States)

John F. Dwyer; David J. Nowak

2003-01-01

The significance of the urban forest resource and the powerful forces for change in the urban environment make sustainability a critical issue in urban forest management. The diversity, connectedness, and dynamics of the urban forest establish the context for management that will determine the sustainability of forest structure, health, functions, and benefits. A...

Sustainability in the textile industry

CERN Document Server

2017-01-01

This book examines in detail key aspects of sustainability in the textile industry, especially environmental, social and economic sustainability in the textiles and clothing sector. It highlights the various faces and facets of sustainability and their implications for textiles and the clothing sector.

Viral Innovation, Sustainability, and Excellence

DEFF Research Database (Denmark)

Edgeman, Rick; Eskildsen, Jacob Kjær

Enterprises strive to be economically sustainable. In doing so, they either contribute to or detract from environmental and social sustainability. Sustainability is hence multi-dimensional with formulations that include the familiar triple-bottom-line and BEST models. Any assessment regimen for t...

Sustainability in Modern Art Museums

DEFF Research Database (Denmark)

Campolmi, Irene

2013-01-01

The paper analyzes the concept of sustainability in European governmental museum policies. It takes into consideration great modern art museums, particularly Tate Modern. On the one hand, the issue of sustainability is linked to art museums inasmuch these institutions operate for the sustainable...... to their eligibility for funding and it is indeed an economic rather than a cultural issue. Though, modern art museums’ sustainability relies not only in developing economic and environmental strategies but mostly in creating cultural policies that favor art museums in accomplishing same tasks but from different...... curatorial and managerial perspectives. A long-term sustainable museum model steps beyond Foucault’s notion that art museums are “heterotopy”, i.e. spaces that present art as an alternative phenomenon outside reality. On the contrary, a sustainable model for museums acts as “archètopy”, i.e. a space (tòpos...

Leverage points for sustainability transformation.

Science.gov (United States)

Abson, David J; Fischer, Joern; Leventon, Julia; Newig, Jens; Schomerus, Thomas; Vilsmaier, Ulli; von Wehrden, Henrik; Abernethy, Paivi; Ives, Christopher D; Jager, Nicolas W; Lang, Daniel J

2017-02-01

Despite substantial focus on sustainability issues in both science and politics, humanity remains on largely unsustainable development trajectories. Partly, this is due to the failure of sustainability science to engage with the root causes of unsustainability. Drawing on ideas by Donella Meadows, we argue that many sustainability interventions target highly tangible, but essentially weak, leverage points (i.e. using interventions that are easy, but have limited potential for transformational change). Thus, there is an urgent need to focus on less obvious but potentially far more powerful areas of intervention. We propose a research agenda inspired by systems thinking that focuses on transformational 'sustainability interventions', centred on three realms of leverage: reconnecting people to nature, restructuring institutions and rethinking how knowledge is created and used in pursuit of sustainability. The notion of leverage points has the potential to act as a boundary object for genuinely transformational sustainability science.

Non-Thermal Plasma Treatment Diminishes Fungal Viability and Up-Regulates Resistance Genes in a Plant Host

Science.gov (United States)

Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha

2014-01-01

Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance. PMID:24911947

Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke

Directory of Open Access Journals (Sweden)

Gongwei Jia

2017-01-01

Full Text Available Background. The role of Peroxiredoxin 6 (Prdx6 in brain ischemia remains unclear. Curcumin (Cur treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1 were involved in the antioxidant effect of Cur after stoke. Methods. Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR, Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A. Results. Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM. Conclusions. Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.

Non-thermal plasma treatment diminishes fungal viability and up-regulates resistance genes in a plant host.

Directory of Open Access Journals (Sweden)

Kamonporn Panngom

Full Text Available Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance.

Compendium of Environmental Sustainability Indicator Collections: Rio to Johannesburg Dashboard of Sustainable Indicators

Data.gov (United States)

National Aeronautics and Space Administration — The Rio to Johannesburg Dashboard of Sustainable Development Indicators portion of the Compendium of Environmental Sustainability Indicator Collections contains 35...

The road to sustainability

Energy Technology Data Exchange (ETDEWEB)

Sarrao, John L [Los Alamos National Laboratory; Crabtree, George [ANL

2009-01-01

Sustainability is the hottest topic in energy research today, but what does it actually mean? George Crabtree and John Sarrao describe what makes a technology sustainable, and outline the materials-science challenges standing between us and clean, long-lasting energy. Although most people agree that more-sustainable energy technologies are desirable, they often find it harder to agree on exactly how sustainable these technologies need to be, and even precisely what is meant by sustainability. To clarify the debate, we suggest three criteria for sustainability, each of which captures a different feature of the problem. While we do not have the lUxury of achieving full sustainability for all of our next-generation energy technologies, we can use these definitions to select our strategic sustainability targets and track our progress toward achieving them. As will become clear, the most sustainable energy technologies require the most challenging fundamental science breakthroughs. The first criterion for sustainability is 'lasts a long time'. This quality has been a feature of many energy sources we have used historically, including wood in ancient times and oil throughout most of the 20th century. The definition of 'long time' is, of course, relative: the world's demand for energy long ago outpaced the ability of wood to supply it, and the production of oil is likely to peak sometime within the next few decades. Substantial reductions in the rate of oil consumption through higher-efficiency processes can significantly impact on how long non-renewable resources last. In applying the 'long time' criterion, we need to distinguish between energy sources that are effectively limitless and those that are finite but, for the moment, adequate. The second criterion for sustainability is 'does no harm'. Burning fossil fuels releases pollutants such as sulphur and mercury that endanger human health, as well as greenhouse gases like

Education for Sustainable Development at the United Nations Conference on Sustainable Development (Rio+20)

Science.gov (United States)

Journal of Education for Sustainable Development, 2012

2012-01-01

The United Nations Conference on Sustainable Development (Rio+20) was held in Rio de Janeiro, Brazil, 20-22 June 2012, marking the twentieth anniversary of the United Nations Conference on Sustainable Development in Rio de Janeiro in 1992 and the tenth anniversary of the 2002 World Summit on Sustainable Development in Johannesburg. With more than…

Use and usefulness of sustainability economics

Energy Technology Data Exchange (ETDEWEB)

Bartelmus, Peter [Bergische Universitaet Wuppertal (Germany)

2010-09-15

Sustainable development is at the roots of sustainability economics. Baumgaertner and Quaas (2010) define sustainability economics as the combination of economic efficiency and justice in the distribution of nature's services. Van den Bergh (in press) criticizes their approach as 'axiomatic' and incomplete, lacking a discussion of environmental externalities and dogmas like the 'GDP dogma'. The focus on non-measurable welfare or happiness in both articles impairs the use and usefulness of their sustainability notions for applied economics and policy. Alternatively, environmentally modified national accounts offer a quantifiable sustainability concept of produced and natural capital maintenance. For practical reasons, sustainability economics should therefore deal with sustainable economic performance and growth. Coordination with other social goals has to be left to politics. (author)

Sustainability-open : Why every building will be sustainable in the future

NARCIS (Netherlands)

Coenders, J.L.

2013-01-01

In this paper the initiative “sustainability-open” will be introduced. The aim of the initiative is to take away one of the reasons why buildings and other objects in the built environment are often not designed in a sustainable manner: the availability of clear and insightful software to analyse

Correlation between Sustainability Education and Engineering Students' Attitudes towards Sustainability

Science.gov (United States)

Tang, Kuok Ho Daniel

2018-01-01

Purpose: The purpose of this study is to investigate the impacts of a sustainable development course on the beliefs, attitudes and intentions of a cohort of engineering students in a university in Miri, Malaysia, towards sustainability. Design/methodology/approach: Questionnaire survey was conducted among the cohort of students encompassing the…

Adopting Sustainability in the Organization

DEFF Research Database (Denmark)

Frandsen, Sanne; Morsing, Mette; Vallentin, Steen

2013-01-01

Purpose – The purpose of this paper is to explore the relationship between sustainability adoption and internal legitimacy construction. Design/methodology/approach – The paper is designed as a critical inquiry into existing research and practice on sustainability adoption, illustrated by two...... corporate vignettes. Findings – Prior studies tend to assume that awareness raising is a sufficient means to create employee commitment and support for corporate sustainability programs, while empirical observations indicate that managerial disregard of conflicting interpretations of sustainability may...... result in the illegitimacy of such programs. Originality/value – The authors suggest that a loosely coupled approach to sustainability adoption is a productive way to understand internal legitimacy construction, as it appreciates complexity and polyphony....

Sustainability in the Business Case

NARCIS (Netherlands)

Ron Schipper; Gilbert Gilbert Silvius

2012-01-01

This paper explores the integration of indicators that reflect the concepts of sustainability into business cases and business case evaluation methods. It is based on the observations that sustainability is one of the most important challenges of our time and that sustainable development requires

Sustainability curricula in design education

NARCIS (Netherlands)

Casais, M.; Christiaans, H.H.C.M.; Almendra, R.

2012-01-01

While sustainability in Design finds much attention in the literature, the education of sustainability in Design courses lacks discussion regarding curricula and importance. In an attempt to map the way sustainability is taught in Design Bachelor and Master Courses in the European Union, we began

Cork for sustainable product design

NARCIS (Netherlands)

Mestre, A.C.; Gil, L.

2011-01-01

Sustainable Product Design is currently accepted as one of the most promising trends in the “Sustainable Development” movement. It is often seen as a facilitation tool to implement Sustainability in practice, by improving the life cycle and eco-efficiency of products, by promoting dematerialization

Mobilizing consumer demand for sustainable development

NARCIS (Netherlands)

Trijp, van J.C.M.; Fischer, A.R.H.

2011-01-01

A lot of innovation effort is aimed at increased sustainable consumption, while at the same time actual sustainable consumption is not meeting the expectations raised by the positive public attitudes towards sustainability. This is indicative of a gap between attitudes and behaviors in sustainable

Sustainable development. First part

International Nuclear Information System (INIS)

Colombo, U.; Lanzavecchia, G.; Berrini, M; Zambrini, M.; Bologna, G.; Carraro, C.; Hinterberger, F.; Mastino, G.; Federico, A.; Gaudioso, D.; Luise, A.; Mauro, F.; Padovani, L.; Federico, A.

1998-01-01

This paper summarizes a collective effort and represents the second edition of: Environment, energy, economy: a sustainable future. In this work are reported various interventions on sustainable development problem [it

Sustainability Science: Sustainable Energy for Mobility and Its Use in Policy Making

Directory of Open Access Journals (Sweden)

Fabio Orecchini

2011-10-01

Full Text Available Since the 1980s sustainability has clearly become the challenge of the 21st century. In a process toward a sustainable society it is crucial that different stakeholders start collaboration and exchange ideas with technicians and academics. To finalize the policy decisions on important issues such as energy sustainability, collaboration between policy makers, academia and the private sector is important. This work intends to give Italian policy makers concrete advice and solutions to develop energy systems for mobility. The analysis proceeds from the context of Sustainability Science, a new science, which has emerged as one of the most important disciplines of international scientific research. Using a new approach, trans-disciplinary and integrated, this research is oriented to study and understand the complexity of the interactions between economy, society and nature. This broad approach permits proposing concrete solutions to complex problems locally and globally. We propose a scheme of definition of Sustainability Energy, defining five pillars of reference, and we redefine the energy systems for mobility in the context of Sustainability Science. In this paper, we start from the idea that we are living in a crucial passage, we are moving from the era of petroleum to the era of energy vectors. Energy systems, including mobility, should be redefined within this new approach.

Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

NARCIS (Netherlands)

Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

Towards Intelligently - Sustainable Cities?

Directory of Open Access Journals (Sweden)

Luca Salvati

2013-04-01

Full Text Available In the quest for achieving sustainable cities, Intelligent and Knowledge City Programmes (ICPs and KCPs represent cost-efficient strategies for improving the overall performance of urban systems. However, even though nobody argues on the desirability of making cities “smarter”, the fundamental questions of how and to what extent can ICPs and KCPs contribute to the achievement of urban sustainability lack a precise answer. In the attempt of providing a structured answer to these interrogatives, this paper presents a methodology developed for investigating the modalities through which ICPs and KCPs contribute to the achievement or urban sustainability. Results suggest that ICPs and KCPs efficacy lies in supporting cities achieve a sustainable urban metabolism through optimization, innovation and behavior changes.

Towards Sustainable Growth Business Models

Energy Technology Data Exchange (ETDEWEB)

Kamp-Roelands, N.; Balkenende, J.P.; Van Ommen, P.

2012-03-15

The Dutch Sustainable Growth Coalition (DSGC) has the following objectives: The DSGC aims to pro-actively drive sustainable growth business models along three lines: (1) Shape. DSGC member companies aim to connect economic profitability with environmental and social progress on the basis of integrated sustainable growth business models; (2) Share. DSGC member companies aim for joint advocacy of sustainable growth business models both internationally and nationally; and (3) Stimulate. DSGC member companies aim to stimulate and influence the policy debate on enabling sustainable growth - with a view to finding solutions to the environmental and social challenges we are facing. This is their first report. The vision, actions and mission of DSGC are documented in the Manifesto in Chapter 2 of this publication. Chapter 3 contains an overview of key features of an integrated sustainable growth business model and the roadmap towards such a model. In Chapter 4, project examples of DSGC members are presented, providing insight into the hands-on reality of implementing the good practices. Chapter 5 offers an overview of how the Netherlands provides an enabling environment for sustainable growth business models. Chapter 6 offers the key conclusions.

Roundtabling Sustainability

DEFF Research Database (Denmark)

Ponte, Stefano

2014-01-01

councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity...... and procedures to meet ‘good practice’ in standard setting and management. This is opening space for competing initiatives that are less democratic, quicker, and more aligned with industry interests to establish substantial presence in the market for sustainability certifications. These tend to more easily...

Monitor Sustainable Netherlands 2011

International Nuclear Information System (INIS)

2011-09-01

The Monitor provides an image of the sustainability of the Dutch society. It shows which areas are successful and what the 'concerns for tomorrow' are from the point of view of sustainability. An analysis is conducted of how the Netherlands are doing in the fields of climate change, biodiversity, health, knowledge, graying and social cohesion. These and many other topics are discussed in this monitor by means of a number of sustainability indicators and detail analyses [mk]. [nl

Monitor Sustainable Netherlands 2009

International Nuclear Information System (INIS)

2009-02-01

The Monitor provides an image of the sustainability of the Dutch society. It shows which areas are successful and what the 'concerns for tomorrow' are from the point of view of sustainability. An analysis is conducted of how the Netherlands are doing in the fields of climate change, biodiversity, health, knowledge, graying and social cohesion. These and many other topics are discussed in this monitor by means of a number of sustainability indicators and detail analyses [mk] [nl

Managing Supplier Sustainability Risk

OpenAIRE

Harilainen, Hanna-Riitta

2014-01-01

Supply chains are increasingly global, often reaching to developing regions. The media pressure brand owners to be responsible, but a product is only as sustainable as the practices of all the companies involved in manufacturing it are. It’s not enough that the brand owner acts responsibly; sustainable practices have to reach component and raw material suppliers upstream. Image risk has often been recognized as reason for investing in sustainability. In the supply chain context, supplier m...

Sustainability and Organizational Change

OpenAIRE

Sitnikov, Catălina

2012-01-01

The relevant and, above all, remarkable feature of sustainability is due to its "duality": on the one hand, it is an indispensable element within the companies even if, on the other hand, it increases the costs of many activities and processes. Facing the challenge of sustainability will determine and create, in the coming years, emerging organizational forms. If ten years ago, many managers clearly expressed their doubts regarding the financial feasibility of sustainability, today, they admi...

Sustainability protects resources for future generations

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-04-01

This publication by the National Renewable Energy Laboratory addresses the steps necessary to provide livable urban centers for future generations through sustainable development, or sustainability. To illustrate this concept, nonsustainable cities and sustainable cities are compared. Sustainable city projects for several major US cites are reviewed.

Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

Energy Technology Data Exchange (ETDEWEB)

Casado, Enrique, E-mail: enrique.casado@salud.madrid.org [Unidad de Oncologia, Hospital Infanta Sofia, Madrid (Spain); Moreno Garcia, Victor [Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid (Spain); Laboratorio de Oncologia Traslacional, Hospital Universitario La Paz, Madrid (Spain); Sanchez, Jose Javier [Departamento de Bioestadistica, Universidad Autonoma de Madrid, Madrid (Spain); Gomez del Pulgar, Maria Teresa [Unidad de Oncologia Traslacional, Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas, Madrid (Spain); Feliu, Jaime [Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid (Spain); Laboratorio de Oncologia Traslacional, Hospital Universitario La Paz, Madrid (Spain); Maurel, Joan [Departamento de Oncologia, Hospital Clinic, Barcelona (Spain); Castelo, Beatriz [Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid (Spain); Moreno Rubio, Juan; Lopez, Rocio A.B. [Laboratorio de Oncologia Traslacional, Hospital Universitario La Paz, Madrid (Spain); Garcia-Cabezas, Miguel Angel; Burgos, Emilio [Departamento de Anatomia Patologica, Hospital Universitario La Paz, Madrid (Spain); and others

2012-12-01

Purpose: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. Methods: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. Results: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. Conclusion: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.

Demonstrating sustainable energy: A review-based model of sustainable energy demonstration projects

NARCIS (Netherlands)

Bossink, Bart

2017-01-01

This article develops a model of sustainable energy demonstration projects, based on a review of 229 scientific publications on demonstrations in renewable and sustainable energy. The model addresses the basic organizational characteristics (aim, cooperative form, and physical location) and learning

Development of Sustainable Rural Tourism

Directory of Open Access Journals (Sweden)

Sandra Kantar

2017-06-01

Full Text Available This paper presents a sociological view of possibilities for the development of sustainable rural tourism in Koprivnica-Krizevci county, which is located in the north-western part of Croatia. The possibilities for developing rural tourism within the concept of sustainable development have been researched through qualitative empirical research interview method. Research subjects were the owners of tourist farms, decision makers, experts and other stakeholders in the tourism development. Rural tourism represents an alternative to maritime tourism and is relatively undeveloped but important in terms of development of rural areas and family farms. This paper enables an insight into an integrated sustainability of rural tourism which consists of four dimensions: biologicalecological, economic, socio-cultural and political sustainability. In conclusion, integral sustainability in rural tourism is not achieved in all dimensions. Therefore, rural tourism could be a strategy for sustainable development for rural areas and also could be a tool for product differentiation for area that are at stagnation stage.

Sustainable development strategy 2001-2003

International Nuclear Information System (INIS)

2001-01-01

The planned strategies and actions that Environment Canada (EC) will take to promote sustainable development with the goal to preserve and enhance the quality of the natural environment and its renewable resources were described. EC's challenge regarding sustainable development is to integrate environmental, economic and social considerations into their federal environmental policies and programs. This report described how EC plans to implement their agenda based on four major themes which include: (1) knowledge for decision making, (2) incentives, (3) partnerships and sustainable communities, and (4) managing for sustainable development. A federal framework on sustainable communities will be developed jointly with other government departments and partners with the objective of developing action plans. EC will measure and report on its performance in implementing its sustainable development strategy on an annual basis to identify any corrective measures during the three year period of the strategy. This report also included an issue scan, a consultation summary, and a review of the department's long term results against performance indicators. tab., figs

Winning the sustainable development debate

International Nuclear Information System (INIS)

Ritch, John; Cornish, Emma

2002-01-01

Full text: This year - in Johannesburg from 26 August to 4 September - the world will witness what is expected to be the largest environmental gathering yet: the World Summit on Sustainable Development. Some 60,000 participants, including Heads of State, government officials, intergovernmental organizations, and environmental, business and scientific lobbies, will debate the world's progress in implementing 'Agenda 2 V - the sustainable development principles agreed in Rio de Janeiro in 1992. Some kind of deal, perhaps in the form of a declaration, will emerge from Johannesburg, reasserting international commitment to sustainable development. At this stage the content cannot be predicted. Experience warns us to expect a strong and virulent anti-nuclear lobby, not only as part of the 'environmental community', but within some of the governments themselves. Their role will be to achieve a text declaring nuclear an unsustainable energy source. The nuclear industry has six months to make its case, in the preparatory fora and elsewhere, that nuclear energy must be recognized - and at a minimum, not excluded - as a sustainable development technology. Twin goals of sustainable development: meeting human need and achieving environmental security. The principle of sustainable development aims at the long-term environmental protection of the planet - sparing our children and their children from living on a planet irredeemably spoilt through human action. An equally pressing issue is that of bridging the wealth gap between the North and South. In this vein, UN Secretary General Kofi Annan recently published his priorities for attention at the World Summit. These include: - Poverty eradication and achieving sustainable livelihoods; - Promoting health through sustainable development; - Access to energy and energy efficiency; - Managing the world's freshwater resources; - Sustainable development initiatives for Africa. The central element of sustainable development: clean energy

Methodology of sustainability accounting

Directory of Open Access Journals (Sweden)

O.H. Sokil

2017-03-01

Full Text Available Modern challenges of the theory and methodology of accounting are realized through the formation and implementation of new concepts, the purpose of which is to meet the needs of users in standard and unique information. The development of a methodology for sustainability accounting is a key aspect of the management of an economic entity. The purpose of the article is to form the methodological bases of accounting for sustainable development and determine its goals, objectives, object, subject, methods, functions and key aspects. The author analyzes the theoretical bases of the definition and considers the components of the traditional accounting methodology. Generalized structural diagram of the methodology for accounting for sustainable development is offered in the article. The complex of methods and principles of sustainable development accounting for systematized and non-standard provisions has been systematized. The new system of theoretical and methodological provisions of accounting for sustainable development is justified in the context of determining its purpose, objective, subject, object, methods, functions and key aspects.